Intratympanic Gentamicin Injection Research Articles

Pharmacological Interventions for Menière's Disease: A Systematic Review and Network Meta-Analysis.

Objective: Evaluation of the effectiveness and posttreatment effects of intratympanic gentamicin and corticosteroids in treating patients with Ménière's disease (MD). Methods: Based on PubMed and Embase databases, randomized controlled trials using intratympanic injections of 4 drugs (gentamicin, methylprednisolone, dexamethasone, and placebo) for the treatment of MD were searched from 1995 to October 2023, and the literature was screened according to inclusion and exclusion criteria, and data were netted for meta-analysis using Stata 17. Results: A total of 13 studies were selected, involving 559 participants, with follow-up time ranging from 3 to 28 months. Meta-analysis showed that there was no statistically significant difference in pure-tone average between gentamicin and dexamethasone [standardized mean difference (SMD) = 0.09, 95% confidence interval (CI) (-0.42, 0.24), P < .05]. Compared to placebo, intratympanic injection of gentamicin [risk ratio (RR) = 1.18, 95% CI (0.43, 1.93)], methylprednisolone [RR = 0.88, 95% CI (0.07, 1.70)], and dexamethasone [RR = 0.70, 95% CI (-0.01, 1.41)] all showed better efficacy in treating vertigo. For the treatment of tinnitus, the SUCRA ranking results showed that dexamethasone was the most effective, followed by methylprednisolone and gentamicin. Conclusion: Pharmacological intervention is more effective than placebo in treating MD. Although gentamicin treatment shows significant effects in treating vertigo, corticosteroid combination therapy is markedly superior to gentamicin in controlling hearing loss and vertigo symptoms.

Preliminary Evidence for the Effects of Gentamicin on Vertical Semicircular Canals

Introduction: Gentamicin is a vestibulotoxic antibiotic often used in patients with Ménière's disease for its vestibular ablative effects. Gentamicin’s effect on the horizontal semicircular canal does not always correlate with the degree of vertigo control achieved by patients; its effect on the vertical semicircular canals remains unknown. We sought to examine the effect of intratympanic gentamicin on vertical semicircular canal function in patients with Ménière's disease using video head impulse testing. Methods: A retrospective case series was carried out at a tertiary academic center. Patients with Ménière's disease who received ≥1 intratympanic gentamicin injection from 2019–2022 and had video head impulse testing performed were included. Outcomes of interest were vertical semicircular canal function following intratympanic gentamicin, correlations between vertical semicircular canal function and horizontal semicircular canal function, and residual symptoms following injection. Results: Ten patients met inclusion criteria. Twenty percent had abnormal V-SCC function prior to any injection and 40% following the first injection. There was an association between abnormal vertical and horizontal semicircular canal function following the first intratympanic gentamicin injection, though the relationship did not reach statistical significance (p = 0.058). While patients with abnormal vertical semicircular canal function following the first injection were less likely to report ongoing vertigo attacks, the relationship was not statistically significant (p = 0.260). Conclusions: Intratympanic gentamicin leads to changes in vertical semicircular canal function in at least a proportion of patients with Ménière's disease. Further study is required to better assess correlations between vertical semicircular canal function and symptom control following intratympanic gentamicin.

Improved Recovery after Vestibular Schwannoma Excision with Intratympanic Gentamicin Prehabilitation.

Translabyrinthine excision of a vestibular schwannoma is associated with acute vestibular failure. Preoperative intratympanic gentamicin (ITG) injections can improve objective balance function after surgery but its clinical benefits remain to be established. Adult patients undergoing translabyrinthine removal of a vestibular schwannoma between January 2014 and February 2018 underwent preoperative vestibular function testing. Patients were divided in to 3 groups, those with vestibular function (VF) who received ITG injections, those with VF but did not receive ITG and those with no VF. Groups were compared according to degree of vertigo, length of stay, time to unassisted mobilization, and postoperative anti-emetic consumption. Forty six patients had ITG injections (Group 1), 7 had residual VF but refused treatment (Group 2), 21 had no VF (Group 3). Group 1 had a significant improvement in vertigo over time whereas groups 2 and 3 did not. There was a statistically significant 70% decrease in time to independent mobilization between Group 1 and other groups and a 19% decrease in length of stay in Group 1 compared to other groups although this did not reach statistical significance. Two patients had injection-related complications. Group 1 used less anti-emetics than other groups but this was not statistically significant. Preoperative intratympanic gentamicin injection with vestibular rehabilitation exercises is associated with less postoperative vertigo and earlier postoperative mobilization. There was reduced duration of hospitalization and decreased consumption of anti-emetic but not significantly so possibly because of low numbers of patients in the no treatment group. 2 Laryngoscope, 134:3316-3322, 2024.

Therapeutic Response of Meniere's Disease Utilizing Sorbus domestica.

Introduction Meniere's disease (MD) is a chronic condition characterized by episodic attacks of vertigo, fluctuating hearing loss, and tinnitus. MD can impart a significant socioeconomic impact with associated progressive hearing loss. First-line therapies consist of diuretics and antihistamines, with second-line therapies including intratympanic steroids and pulse therapy. Third-linetreatments include endolymphatic sac surgery (ELSS) followed by intratympanic gentamicin injection and/or vestibular neurectomy. The gemmotherapy Sorbus domestica's inherent properties to regulate venous circulation and lymphatic drainage have been utilized in the European literature for the treatment of MD and the patients in this study. Methods Patients presenting for rehabilitation at Pulaski Health and Rehabilitation Facility with a history of vertigo were examined and, through history and specific exam, to define MD. This resulted in six patients whose symptoms and exam were consistent with MD and interfered with their therapeutic progression. These patients were offered and accepted treatment with Sorbus domestica for their MD. Results All patients responded with either resolution or significant improvement in their symptoms and hearing loss. Treatment also resulted in an improved and probably shortened rehabilitative course. All patients had no adverse reactions and were supplied with resources for continual treatment upon discharge. Conclusion Sorbus domestica is a safe and viable treatment option for MD. It has been useful, especially in treatment-resistant diseases, without side effects and can be utilized in initial cases with improvement or resolution of hearing loss.

Intratympanic injection for treatment of inner ear diseases

Background: Intratympanic injection has emerged as a novel approach to bypass the blood-labyrinth barrier and effectively deliver drugs into the inner ear. This technique is used for treatment of various inner ear diseases and overcomes the limitations of systemic drug therapy. In this paper, we provide an overview of the application of intratympanic injection using steroids and gentamicin and highlight the major diseases and summarize the reported efficacy of this approach.Current Concepts: Intratympanic steroid injections have been used for treatment of various inner ear diseases, including sudden sensorineural hearing loss, Ménière disease, and tinnitus. Therapeutic effects of steroids include reducing inflammation, modulating the immune response, improving cochlear blood flow, and maintaining ion homeostasis. Intratympanic gentamicin injections are primarily used to minimize hearing loss and control vertigo symptoms in patients with Ménière disease. Gentamicin selectively injures vestibular hair cells with minimal ototoxicity compared with other aminoglycoside antibiotics.Discussion and Conclusion: Intratympanic injections offer several advantages, including targeted drug delivery, minimal systemic adverse effects, and rapid action. Reportedly, intratympanic steroid injections used as primary or salvage treatment are associated with positive outcomes in patients with sudden sensorineural hearing loss. Ménière disease also shows positive outcomes following intratympanic steroid and gentamicin injections. However, studies have reported conflicting results, and further research is required to standardize dosing and administration protocols. Intratympanic injections are a promising therapeutic option, and ongoing research is essential to optimize their efficacy and safety.

Prosthetic Stimulation of the Vestibular Nerve Can Evoke Robust Eye and Head Movements Despite Prior Labyrinthectomy.

Prosthetic electrical stimulation can evoke compensatory eye and head movement despite vestibular implant electrode insertion occurring years after prior labyrinthectomy. Vestibular implants sense head rotation and directly stimulate the vestibular nerve, bypassing damaged end organs. Animal research and current clinical trials have demonstrated the efficacy of this approach. However, candidacy criteria for vestibular implants currently require presence of a patent labyrinth in the candidate ear and at least aidable hearing in the opposite ear, thus excluding patients who have undergone prior labyrinthectomy for unilateral Menière's disease that later progressed to bilateral vestibular hypofunction. Eight years after right unilateral labyrinthectomy, we implanted stimulating electrodes in the previously exenterated right ear ampullae of a rhesus macaque monkey. The left labyrinth had long-standing hypofunction due to intratympanic gentamicin injection and surgical disruption. We used three-dimensional video-oculography to measure eye movement responses to prosthetic electrical stimulation. We also measured head-movement responses to prosthetic stimulation with the head unrestrained. Bilateral vestibular hypofunction was confirmed by absence of vestibuloocular reflex responses to whole-body rotation without prosthetic stimulation. For a subset of the implanted electrodes, prosthetic vestibular stimulation evoked robust compensatory eye and head movements. One electrode reliably elicited responses aligned with the implanted ear's anterior canal nerve regardless of the return electrode used. Similarly, a second electrode also elicited responses consistent with excitation of the horizontal canal nerve. Responses grew quasilinearly with stimulation rate and current amplitude. Prosthetic electrical stimulation targeting the vestibular nerve can be effective years after labyrinthectomy, if at least some parts of the vestibular nerve's ampullary branches remain despite destruction or removal of the membranous labyrinth.

Binocular 3-D otolith-ocular reflexes: responses of chinchillas to natural and prosthetic stimulation after ototoxic injury and vestibular implantation.

The otolith end organs inform the brain about gravitational and linear accelerations, driving the otolith-ocular reflex (OOR) to stabilize the eyes during translational motion (e.g., moving forward without rotating) and head tilt with respect to gravity. We previously characterized OOR responses of normal chinchillas to whole body tilt and translation and to prosthetic electrical stimulation targeting the utricle and saccule via electrodes implanted in otherwise normal ears. Here we extend that work to examine OOR responses to tilt and translation stimuli after unilateral intratympanic gentamicin injection and to natural/mechanical and prosthetic/electrical stimulation delivered separately or in combination to animals with bilateral vestibular hypofunction after right ear intratympanic gentamicin injection followed by surgical disruption of the left labyrinth at the time of electrode implantation. Unilateral intratympanic gentamicin injection decreased natural OOR response magnitude to about half of normal, without markedly changing OOR response direction or symmetry. Subsequent surgical disruption of the contralateral labyrinth at the time of electrode implantation surgery further decreased OOR magnitude during natural stimulation, consistent with bimodal-bilateral otolith end organ hypofunction (ototoxic on the right ear, surgical on the left ear). Delivery of pulse frequency- or pulse amplitude-modulated prosthetic/electrical stimulation targeting the left utricle and saccule in phase with whole body tilt and translation motion stimuli yielded responses closer to normal than the deficient OOR responses of those same animals in response to head tilt and translation alone.NEW & NOTEWORTHY Previous studies to expand the scope of prosthetic stimulation of the otolith end organs showed that selective stimulation of the utricle and saccule is possible. This article further defines those possibilities by characterizing a diseased animal model and subsequently studying its responses to electrical stimulation alone and in combination with mechanical motion. We show that we can partially restore responses to tilt and translation in animals with unilateral gentamicin ototoxic injury and contralateral surgical disruption.

Skull-vibration-induced nystagmus test in patients who are candidates for intratympanic gentamicin injection

This study aims to evaluate the utility of the skull-vibration-induced nystagmus test (SVINT) in the selection of patients with Ménière's disease (MD) for intratympanic injection of gentamicin. To date the indications for this treatment have been based only on subjective elements. A retrospective study was performed in 20 patients diagnosed with unilateral MD. SVINT were performed monthly and the evoked responses were evaluated. After 6 months, the results from patients who were candidates for gentamicin treatment (G group) were compared with those who did not need it (nG group). Correlation with Dizziness Handicap Inventory (DHI) score was evaluated. 120 tests were performed. Positive SVINTs were identified in 52 cases (43.3%) and included excitatory nystagmus in 18 (34.7%), inhibitory nystagmus in 28 (53.8%), and atypical pattern in 6 cases (11.5%). A significant increase excitatory nystagmus was recorded in group G (p = 0.00001). Moreover, there was a significant increase in the DHI score in group G compared with the nG group (p < 0.0001) and in patients with evoked excitatory nystagmus. The finding of excitatory nystagmus during SVINTs performed on several occasions in the follow-up prior to intratympanic injection of gentamicin strengthens this therapeutic choice.

A bibliometric and visualization study of Meniere's disease: Current status and global hotspots and emerging trends.

Meniere's disease (MD) is a clinical condition characterized by endolymphatic hydrops. Persistent symptoms negatively affect patients mood, and the underlying etiology remains unclear. It is necessary to comprehensively understand the relevant publications, review the history and current status of research, and analyze hotspots and frontiers of research on MD. We retrieved literature on Meniere's disease from 2003 to 2022 from the Web of Science database and extracted the data. Data visualization and analysis was conducted using Cite Space, VOS viewer, an online web tool, and Microsoft Office Power Point 2019. In total, 2847 publications were analyzed. The number of annual publications was relatively stable, with an accelerated upward trend over the past 5 years. The country with the most publications was USA (751, 26.38%), while the University of Munich contributed more publications than any other institution (117, 4.11%). The article titled "Diagnostic criteria for Meniere's disease" by Lopez-Escamez J et al in 2015 was the most cited and co-cited publication, and also had the top co-cited references with the strongest citation bursts. Naganawa S was the author with the most publications (85, 2.99%). The top 3 journals and co-cited journals were Otology Neurotology, Acta Oto Laryngologica, and Laryngoscope. Recently, the key theme words were "sensorineural hearing loss," "therapy," "intratympanic injection method," "vestibular-evoked myogenic potentials," "vestibular migraine," "magnetic resonance imaging," and "meniere's disease." The US has the largest number of publications and research institutions, many European countries have high-quality journals, and Japan has the highest number of scholars. The international opinion on Meniere's disease is relatively uniform. The stepped-therapy for MD is scientific and clear. Intratympanic injection of steroids and intratympanic injection of gentamicin are commonly used, but steroids are considered safer. Saccular dysfunction may be more common in patients with MD than in those with utricular dysfunctions. It is worth paying attention to study the relationship between MD and vestibular migraine through headache. Progress in magnetic resonance imaging technology is still required for the imaging diagnosis of MD.

Intratympanic Gentamicin Injection for Treatment of Vertigo in Intractable Meniere's Disease

Intratympanic Gentamicin Injection for Treatment of Vertigo in Intractable Meniere's Disease

Long-term efficacy of vestibular neurotomy in disabling Ménière's disease and Tumarkin drop attacks.

When Ménière's disease (MD) becomes disabling due to the frequency of attacks or the appearance of drop attacks (i.e., Tumarkin otolithic crisis) despite "conservative" medical and surgical treatments, a radical treatment like vestibular neurotomy (VN) is possible. An ideal MD treatment would relieve symptoms immediately and persist after the therapy. The aim of this study was to identify if VN was effective after 10 years of follow-up regarding vertigo and drop attacks, and to collect the immediate complications. The authors report a retrospective, single-center (i.e., in a single tertiary referral center with otoneurological surgery activity) cohort study conducted from January 2003 to April 2020. All patients with unilateral disabling MD who had received a VN with at least 10 years of follow-up were included. The therapeutic efficacy was defined by complete disappearance of vertigo and drop attacks. The postoperative complications (CSF leak, total deafness, meningitis, death) were determined immediately after the surgery, and the hearing thresholds were determined during the patient follow-up with the pure tone average (PTA). A total of 74 patients (of 85 who were eligible), average age 51.9 ± 11.1 years, including 38 men (51.4%), with disabling MD and/or Tumarkin drop attacks (24.3%) received VN, with at least 10 years of follow-up after surgery. After an average follow-up of 12.4 ± 1.7 years (range 10.0-16.3 years), 67 patients (90.5%) no longer presented any vertiginous attacks, and no patient experienced drop attack. The mean variation in early pre- and postoperative PTA was not statistically significant (n = 64, 2.2 ± 10.3 decibels hearing level [range -18 to 29], 95% CI [-0.4 to 4.37]; p = 0.096), and 84.4% of the patients evaluated had unchanged or improved postoperative PTA. Three significant complications were noted, including two surgical revisions for CSF leak. There was no permanent facial paralysis, meningitis, or death. In case of disabling MD (disabling vertigo refractory to conservative vestibular treatments-Tumarkin drop attacks), VN via the retrosigmoid approach must be the prioritized proposal in comparison to intratympanic gentamicin injections, because of the extremely low complication rate and the immediate and long-lasting effect of this treatment on vertigo and falls.

Low-Dose Intratympanic Gentamicin for Unilateral Ménière's Disease: Accuracy of Early Vestibulo-Ocular Reflex Gain Reduction in Predicting Long-Term Clinical Outcome.

BackgroundThe number of intratympanic gentamicin (ITG) injections needed to achieve vertigo control in patients with intractable Ménière's disease (MD) may vary from a single dose to several instillations. Changes in different vestibular test results have been used to define an endpoint of treatment, including the decrease of the vestibulo-ocular reflex (VOR) gain elicited by the head-impulse test.ObjectiveTo assess the accuracy of the VOR gain reduction after horizontal canal stimulation, as measured with the video head-impulse test (vHIT) 1 month after the first intratympanic injection, in predicting the need for one or more instillations to control vertigo spells in the long term.MethodsThe VOR gain reduction was calculated in 47 patients submitted to (ITG) therapy 1 month after the first instillation.ResultsSingle intratympanic treatment with gentamicin has a 59.6% efficacy in vertigo control in the long term. Hearing change in the immediate period after treatment (1 month) is not significant to pre-treatment result and is similar for patients who needed multiple doses due to recurrence. Chronic disequilibrium and the need for vestibular rehabilitation were less frequent in patients with a good control of vertigo with just one single injection of gentamicin. A fair accuracy was obtained for the VOR gain reduction of the horizontal canal (area under the curve = 0.729 in the Receiver Operating Characteristic analysis) in predicting the need for one or more ITG.ConclusionsSingle intratympanic treatment with gentamicin is an effective treatment for patients with MD. That modality of treatment has very limited damaging effect in hearing. The degree of vestibular deficit induced by the treatment is significant as measured by the reduction in the gain of the VOR but not useful for prognostic purposes.

Postural stability and handicap of dizziness after preoperative vestibular ablation and vestibular prehabilitation in patients undergoing vestibular schwannoma resection.

Surgical treatment of vestibular schwannoma (VS) leads to acute ipsilateral vestibular loss if there is residual vestibular function before surgery. To overcome the sequelae of acute ipsilateral vestibular loss and to decrease postoperative recovery time, the concept of preemptive vestibular ablation with gentamicin and vestibular prehabilitation before surgery has been developed ("vestibular prehab"). Studying postural stability during walking and handicap of dizziness over a 1-year follow-up period in VS patients undergoing vestibular prehab before surgical treatment of VS. A retrospective review of consecutive patients with a diagnosis of a VS undergoing surgical therapy from June 2012 to March 2018 was performed. All patients were included with documentation of the length of hospital duration and the Dizziness Handicap Inventory (DHI) and the Functional Gait Assessment (FGA) assessed preoperatively as well as 6 weeks and 1 year postoperatively. A total 68 VS patients were included, of which 29 patients received preoperative vestibular ablation by intratympanic injection of gentamicin. Mean VS diameter was 20.2 mm (SD 9.4 mm) and mean age at surgery was 49.6 years (SD 11.5 years). Vestibular prehab had no effect on DHI and FGA at any time point studied. We found no effect of vestibular prehab on postural stability during walking and on the handicap of dizziness. These findings add to the body of knowledge consisting of conflicting results of vestibular prehab. Therefore, vestibular prehab should be applied only in selected cases in an experimental setting.

Intratympanic gentamicin injections

Office-based intratympanic gentamicin injections are an important treatment modality for the management of refractory vestibular symptoms in patients suffering from Meniere's disease. Taking advantage of gentamicin's preferential vestibulotoxicity, chemical labyrinthectomy can be performed. Preprocedural counseling is necessary to ensure that patients have failed symptom control with maximal, non-ablative treatment options, including diet/lifestyle modification, diuretics and intratympanic steroid injections. Additionally, they should be familiar with the risk of hearing loss, and the likely continuation of non-vestibular aural symptoms. With appropriate dosing and monitoring, relief from vestibular symptoms may be achieved in up to 90% of patients while limiting risk to hearing.

Intratympanic gentamicin injection for refractory ménière's disease (MD) has potential effect in preventing contralateral MD occurrence

Background Ménière's disease (MD), characterized by episodic vertigo attacks and fluctuating progressive hearing loss, is treated by low-dose intratympanic gentamicin (ITG) injections. Whether ITG causes hearing loss is controversial, and knowledge about its effects on the contralateral hearing and vestibular function is lacking. Aims/Objectives We aimed to evaluate the effect of ITG on bilateral auditory and otolith organ function in patients with unilateral refractory MD. Material and Methods The data of 30 patients was collected, including history, and pure tone audiometry and vestibular-evoked myogenic potentials (VEMPs) results before and one month after ITG treatment. Changes in vertigo were assessed at a two-year follow-up. Results One month after ITG injection, auditory thresholds between 125 Hz and 8 kHz on the injection side remained unchanged but have improved on the contralateral side at 125 Hz, 250 Hz, 1 kHz. The cervical and ocular VEMP solicitation rates on the injection side were lower than before the injection. Two years after treatment, vertigo was improved in 88.5% and complete controlled in 76.7% patients respectively. Conclusions and Significance The intractable vertigo of MD can be effectively controlled by ITG injection. This can improve the low and medium frequency hearing level in the contralateral ear, suggesting that it might help prevent contralateral MD occurrence.

Protective Effects of Deferoxamine on Vestibulotoxicity in Gentamicin-Induced Bilateral Vestibulopathy Rat Model.

Introduction: Administration of aminoglycoside (AG) antibiotics is one of the most common causes of ototoxicity. This study aimed to determine the protective effects of deferoxamine, an iron-chelating agent, on vestibulotoxicity using an intratympanic gentamicin injection (ITGM)-induced bilateral vestibulopathy rat model.Methods: Fifteen Sprague-Dawley rats were randomly assigned to the ITGM only (n = 5), the ITGM combined with intramuscular deferoxamine (DFO) injection (ITGM+DFO, n = 5), or the intratympanic normal saline (control, n = 5) group. The rats in the ITGM+DFO group received intramuscular injection of 150 mg/kg of deferoxamine at 30, 90, and 150 min after the ITGM. The vestibular function was evaluated using the rotarod and open field test every 3 days after the injection until Day 16 when the rats were subjected to histological changes.Results: The rats in the ITGM only group began to show significantly impaired vestibular function 2 days after ITGM into both ears. In contrast, the vestibular function was maintained in the control and ITGM+DFO groups without a difference throughout the experiments. The rats in the ITGM only group showed a near-complete loss of the type I and II hair cells and a collapse of the sensory epithelium in both the saccule and utricle. In contrast, the rats in the ITGM+DFO and control groups showed a relatively well-preserved sensory epithelium including the hair cells, cilia, and otolith layer.Conclusion: This study provides experimental evidence for preventive effects of iron-chelating agents on AG-induced vestibulotoxicity. Simultaneous administration of iron-chelating agents may be considered when using ototoxic agents, especially in those considered to be vulnerable to toxic damage of the inner ear.

Management of vestibular dysfunction and hearing loss in intralabyrinthine schwannomas

PurposeIntralabyrinthine schwannomas (ILS) are rare, benign, slow-growing tumors arising from schwann cells of the cochlear or vestibular nerves within the bony labyrinth. This study provides insight into the management of this rare tumor through a large case series. Materials and methodsAfter Institutional Review Board approval, a retrospective chart review was performed of all ILS patients treated at our institution between 2007 and 2019. Results20 patients (9 male, 11 female) with ILS were managed at our institution. The right ear was affected in 9 patients (45%) and the left in 11 (55%). Subjective hearing loss was endorsed by all 20 patients. Average pure tone average at presentation was 72 dB nHL. Nine tumors (45%) were intravestibular, 6 (30%) were intracochlear, 4 (20%) were transmodiolar and 1 (5%) was intravestibulocochlear. Hearings aids were used in 3 patients (15%), BiCROS in 2 (10%), CI in 2 (10%), and bone conduction implant in 1 (5%). Vestibular rehabilitation was pursued in 5 patients. Surgical excision was performed for one patient (5%) via translabyrinthine approach due to intractable vertigo. No patients received radiotherapy or intratympanic gentamicin injections. ConclusionILS presents a diagnostic and management challenge given the similarity of symptoms with other disorders and limited treatment options. Hearing loss may be managed on a case-by-case basis according to patient symptoms while vestibular loss may be mitigated with vestibular therapy. Surgical excision may be considered in patients with intractable vertigo, severe hearing loss with concurrent CI placement, or in other case-by-case situations.

Endolymphatic Hydrops in Patients With Intralabyrinthine Schwannomas.

Purpose: The presence of endolymphatic hydrops (EH) in patients with intralabyrinthine schwannomas (ILSs) is poorly understood. This study aims to determine whether there is a correlation between endolymphatic hydrops and clinical presentations of ILS.Methods: Data from nine patients with ILSs were retrospectively reviewed between 2007 and 2020. Temporal bone MRI with intratympanic or intravenous injection of gadolinium was applied to detect ILSs and EH.Results: 3D real inversion recovery (IR) sequence MRI of the temporal bone confirmed ipsilateral EH in four patients (4/6). All four patients with EH on MRI presented with vertigo similar to Meniere's disease. Among these patients with EH, one patient with EH in the cochlea showed moderate sensorineural hearing loss, while three patients with EH in both the vestibule and cochlea showed profound hearing loss. MRI demonstrated a transmacular tumor (TMA) in one patient, intravestibular (IV) in four patients, and vestibulocochlear (VC) in four patients. Two IV cases showed moderated hearing loss, while the TMA and VC cases showed profound hearing loss. Transotic resection of the tumor was applied in five patients; translabyrinthine resection was applied in one patient; two patients were under observation; and one patient was given intratympanic injection of gentamicin (ITG). During follow-up, all of the treated patients reported relief of vertigo, and postoperative MRI was performed in two patients, which showed no tumor recurrence. The two patients under observation showed no deterioration of hearing loss or vertigo. One patient was lost to follow-up.Conclusion: EH concurrent with ILSs has been underestimated previously. With the extensive application of temporal bone MRI paradigms, such as 3D-real IR sequence MRI, more cases of potential EH in patients with ILS will be identified. The severity of hearing loss may be associated with the location of the tumor and the degree of EH.

Hair cell uptake of gentamicin in the developing mouse utricle.

Intratympanic injection of gentamicin has proven to be an effective therapy for intractable vestibular dysfunction. However, most studies to date have focused on the cochlea, so little is known about the distribution and uptake of gentamicin by the counterpart of the auditory system, specificallyvestibular hair cells (HCs). Here, with a combination of in vivo and in vitro approaches, we used a gentamicin-Texas Red (GTTR) conjugate to investigate the mechanisms of gentamicin vestibulotoxicity in the developing mammalian utricular HCs.In vivo, GTTR fluorescence was concentrated in the apical cytoplasm and the cellular membrane of neonatal utricular HCs, but scarce in the nucleus of HCs and supporting cells. Quantitative analysis showed the GTTR uptake by striolar HCs was significantly higher than that in the extrastriola. In addition, the GTTR fluorescence intensity in the striola was increased gradually from 1 to 8 days, peaking at 8-9 days postnatally. In vitro, utricle explants were incubated with GTTR and candidate uptake conduits, including mechanotransduction (MET) channels and endocytosis in the HC, were inhibited separately. GTTR uptake by HCs could be inhibited by quinine, a blocker of MET channels, under both normal and stressed conditions. Meanwhile, endocytic inhibition only reduced GTTR uptake in the CoCl2 hypoxia model. In sum, the maturation of MET channels mediated uptake of GTTR into vestibular HCs. Under stressed conditions, MET channels play a pronounced role, manifested by channel-dependent stress enhanced GTTR permeation, while endocytosis participates in GTTR entry in a more selective manner.

Contralateral spreading of substances following intratympanic nanoparticle-conjugated gentamicin injection in a rat model

This study was performed to investigate the Eustachian tube as a potential route for contralateral spreading following intratympanic nanoparticle (NP)-conjugated gentamicin injection in a rat model. Sprague–Dawley rats were divided into three groups and substances were injected in the right ear: group 1 (fluorescent magnetic nanoparticles [F-MNPs], n = 4), group 2 (F-MNP-conjugated gentamicin [F-MNP@GM], n = 2), and control group (no injections, n = 2). T2-weighted sequences corresponding to the regions of interest at 1, 2, and 3 h after intratympanic injection were evaluated, along with immunostaining fluorescence of both side cochlea. The heterogeneous signal intensity of F-MNPs and F-MNP@GM on T2-weighted images, observed in the ipsilateral tympanum, was also detected in the contralateral tympanum in 4 out of 6 rats, recapitulating fluorescent nanoparticles in the contralateral cochlear hair cells. Computational simulations demonstrate the contralateral spreading of particles by gravity force following intratympanic injection in a rat model. The diffusion rate of the contralateral spreading relies on the sizes and surface charges of particles. Collectively, the Eustachian tube could be a route for contralateral spreading following intratympanic injection. Caution should be taken when using the contralateral ear as a control study investigating inner-ear drug delivery through the transtympanic approach.