Correlation of endolymphatic hydrops and perilymphatic enhancement with the clinical features of Ménière's disease.

OBJECTIVES: To use three-dimensional real inversion recovery (3D-real IR) MRI to investigate correlations between endolymphatic hydrops (EH) grades or the degree of perilymphatic enhancement (PE) and clinical features of Ménière's disease (MD), as previous findings have been inconsistent. METHODS: A total of 273 consecutive patients with definite unilateral MD were retrospectively enrolled from September 2020 to October 2021. All patients underwent 3D-real IR and 3D-T2WI 6 h after intravenous gadolinium injection. MD-related symptom duration and vertigo frequency were recorded. EH grades were evaluated, the signal intensity ratio (SIR) was measured, and correlations between clinical features and EH, PE were assessed respectively. RESULTS: The study included 123 males and 150 females, with a mean age of 53.0 years. A longer duration of vertigo was associated with higher cochlear EH grades, whereas the opposite was true for the duration of aural fullness. A longer time since vertigo onset was associated with higher vestibular EH grades; the opposite was true for the duration of individual vertigo attacks. The multiple regression analysis revealed that age, tinnitus duration, and vestibular EH were risk factors for SIR. Furthermore, the low-frequency hearing threshold (HT) was a risk factor for cochlear and vestibular EH, and the SIR. CONCLUSION: The EH grade and SIR (an indicator for the quantitative evaluation of PE) were correlated with clinical features and HT of MD; thus, imaging can be a valuable tool in planning individualised treatment. CLINICAL RELEVANCE STATEMENT: This study revealed that the grade of endolymphatic hydrops and degree of perilymphatic enhancement positively correlates with the length of time since onset of clinical symptoms and hearing thresholds in patients with Ménière's disease, facilitating the tailored treatment. KEY POINTS: • Relationships between 3-dimensional real inversion recovery features and clinical symptoms in Ménière's disease are unknown. • Symptom duration and hearing thresholds correlated with endolymphatic hydrops grades and degree of perilymphatic enhancement. • MRI features correlate with MD severity; thus, imaging is valuable for planning tailored treatment.

Intratympanic steroid treatment can reduce ROS and immune response in human perilymph investigated by in-depth proteome analysis.

Intratympanic (IT) steroid treatment is one of the most widely used and effective treatments for inner ear disorders such as sudden sensorineural hearing loss (SNHL). However, a clear mechanism of IT steroids in inner ear recovery has not yet been revealed. Therefore, we investigated proteome changes in extracted human perilymph after steroid treatment. In this study, we applied a tandem mass spectrometry (MS/MS)-based proteomics approach to discover global proteome changes by comparing human perilymph after steroid treatment with non-treated perilymph group. Using liquid chromatography-MS/MS analysis, we selected 156 differentially expressed proteins (DEPs) that were statistically significant according to Student's t-test. Functional annotation analysis showed that upregulated proteins after steroid treatment are related to apoptosis signaling, as well as reactive oxygen species (ROS) and immune responses. The protein-protein interaction (PPI) clusters the proteins associated with these processes and attempts to observe signaling circuitry, which mediates cellular response after IT steroid treatments. Moreover, we also considered the interactome analysis of DEPs and observed that those with high interaction scores were categorized as having equivalent molecular functions (MFs). Collectively, we suggest that DEPs and interacting proteins in human perilymph after steroid treatment would inhibit the apoptotic and adaptive immune processes that may lead to anti-inflammatory effects.

Comparison between 3D SPACE FLAIR and 3D TSE FLAIR in Menière's disease.

PURPOSE: Heavily T2-weighted 3D FLAIR (hT2w-3D-FLAIR) sequence with constant flip angle (CFA) has been reported as being more sensitive to low concentrations of gadolinium (Gd) enabling endolymphatic hydrops (EH) visualization. The purpose of this study was to compare signal-to-noise (SNR) ratio, detection rate of EH, and increased perilymphatic enhancement (PE) as well as diagnostic accuracy in diagnosing definite Menière's disease (MD), using 3D-SPACE FLAIR versus conventional 3D-TSE FLAIR. METHODS: This retrospective study included 29 definite MD patients who underwent a 4-h delayed intravenous (IV) Gd-enhanced 3D-TSE FLAIR and 3D-SPACE FLAIR MRI between February 2019 and February 2020. MR images were qualitatively and quantitatively analyzed twice by 2 experienced head and neck radiologists. Qualitative assessment included grading of cochlear and vestibular EH and visual comparison of PE. Quantitative assessment of PE was performed by placing a region of interest (ROI) and ratio calculation in the basal turn of the cochlea and the brainstem. RESULTS: The intra- and inter-reader reliability for grading of EH and PE was excellent (0.7 < kappa < 0.9) for 3D-SPACE FLAIR and exceeded the values for 3D-TSE FLAIR (0.5 < kappa < 0.9) The combination of EH and visual assessment of PE has the highest diagnostic accuracy in diagnosing definite MD on 3D-SPACE FLAIR with a sensitivity of 0.91 and a specificity of 0.98 resulting in a sensitivity raise of 6% compared to 3D-TSE FLAIR. CONCLUSION: Four-hour delayed IV Gd-enhanced 3D-SPACE FLAIR sequence has a higher sensitivity and reproducibility than 3D-TSE FLAIR for the visualization of EH and increased PE in definite MD patients.

In-depth proteome of perilymph in guinea pig model.

The vast majority of sensorineural hearing loss is caused by impairment of the inner ear cells. Proteomic analysis of perilymph may therefore improve our understanding of inner ear diseases and hearing loss. However, the investigation of the human perilymph proteome was limited due to technical difficulties in perilymph sampling. The guinea pig (Cavia porcellus) is frequently used as an experimental model in preclinical hearing research. In this study, we analyzed samples of perilymph collected from 12 guinea pigs to overcome limited experimental information regarding its proteome. We identified a total of 1413 proteins, establishing a greatly expanded proteome of the previously inferred guinea pig perilymph. This provides a comprehensive proteomic resource for the research community, which will facilitate future molecular-phenotypic studies using the guinea pig as an experimental model of relevance to human inner ear biology.

Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome.

Glucocorticoids are the first-line treatment for sensorineural hearing loss, but little is known about the mechanism of their protective effect or the impact of route of administration. The recent development of hollow microneedles enables safe and reliable sampling of perilymph for proteomic analysis. Using these microneedles, we investigate the effect of intratympanic (IT) versus intraperitoneal (IP) dexamethasone administration on guinea pig perilymph proteome. Guinea pigs were treated with IT dexamethasone (n = 6), IP dexamethasone (n = 8), or untreated for control (n = 8) 6 h prior to aspiration. The round window membrane (RWM) was accessed via a postauricular approach, and hollow microneedles were used to perforate the RWM and aspirate 1 µL of perilymph. Perilymph samples were analyzed by liquid chromatography-mass spectrometry-based label-free quantitative proteomics. Mass spectrometry raw data files have been deposited in an international public repository (MassIVE proteomics repository at https://massive.ucsd.edu/) under data set # MSV000086887. In the 22 samples of perilymph analyzed, 632 proteins were detected, including the inner ear protein cochlin, a perilymph marker. Of these, 14 proteins were modulated by IP, and three proteins were modulated by IT dexamethasone. In both IP and IT dexamethasone groups, VGF nerve growth factor inducible was significantly upregulated compared to control. The remaining adjusted proteins modulate neurons, inflammation, or protein synthesis. Proteome analysis facilitated by the use of hollow microneedles shows that route of dexamethasone administration impacts changes seen in perilymph proteome. Compared to IT administration, the IP route was associated with greater changes in protein expression, including proteins involved in neuroprotection, inflammatory pathway, and protein synthesis. Our findings show that microneedles can mediate safe and effective intracochlear sampling and hold promise for inner ear diagnostics.

[Does sealing the oval window in addition to the round window bring an advantage in reserve therapy of acute idiopathic deafness?] / Bringt die Abdeckung des ovalen Fensters zusätzlich zum runden Fenster bei der Reservetherapie der akuten idiopathischen Ertaubung einen Vorteil?

BACKGROUND: Following sudden unilateral deafness or severe sensorineural hearing loss, patients with unsuccessful intravenous steroid therapy can be treated with explorative tympanotomy with sealing of the round (RW) and/or oval window (OW), due to suspected rupture of the RW with perilymph fistula (PLF) or a fissula ante fenestram (FAF). This study investigated whether additional sealing of the oval window (RW+OW) achieved an improved hearing benefit as compared to sealing of the round window only (RW) . METHODS: This retrospective study investigated 54 patients with acute profound hearing loss who underwent tympanoscopy. Audiometric examinations were performed preoperatively and at two postoperative intervals (1 month and 3-6 months after surgery). In 28 patients, the OW was sealed in addition to the RW. RESULTS: No intraoperatively visible PLF or FAF were reported. Hearing thresholds were significantly reduced in the early postoperative follow-up period and further improvement was observed 3-6 months later. No significant differences between the RW and RW+OW subgroups were seen at either follow-up timepoint. In 65% (Kanzaki criteria) and 74% (Siegel criteria) of patients, partial or complete postoperative hearing improvement was observed. Upon comparing the groups of patients with and without hearing improvement, no statistical significance was found in terms of gender, age, secondary diagnoses, or latency period between symptom onset and surgery. CONCLUSION: Additional sealing of the OW did not lead to significantly better postoperative hearing thresholds. In general, postoperative hearing improvement corresponds to published spontaneous remission rates.

Trauma-induced vestibular dysfunction: Possible functional repair under α1-antitrypsin-rich conditions.

Transient vestibular organ deafferentation, such that is caused by traumatic tissue injury, is presently addressed by corticosteroid therapy. However, restoration of neurophysiological properties is rarely achieved. Here, it was hypothesized that the tissue-protective attributes of α1-antityrpsin (AAT) may promote restoration of neuronal function. Inner ear injury was inflicted by unilateral labyrinthotomy in wild-type mice and in mice overexpressing human AAT. A 2-week-long assessment of vestibular signs followed. All animals responded with peak vestibular dysfunction scores within 4 h after local trauma. While wild-type animals displayed partial or no recovery across 7 days post-injury, AAT-rich group exhibited early recovery: from behavioral score 9-out-of-9 at peak to 4.8 ±â€¯0.44 (mean ±â€¯SD) within 8 h from injury, a time when wild-type mice scored 8.6 ±â€¯0.54 (p < 0.0001), and from vestibular score 15-out-of-15 to 7.8 ±â€¯2.2 within 24 h, when wild-type mice scored 13.0 ±â€¯2.0 (p < 0.01). Thus, recovery and functional normalisation of an injured vestibular compartment is achievable without corticosteroid therapy; expedited tissue repair processes appear to result from elevated circulating AAT levels. This study lays the foundation for exploring the molecular and cellular mediators of AAT within the repair processes of the delicate microscopic structures of the vestibular end organ.

Use of topical fluorescein in the diagnosis and localization of perilymphatic fistula.

OBJECTIVE: The purpose of this video presentation is to demonstrate the effect of intraoperative dilute topical fluorescein in perilympatic fistula diagnosis and localization. MATERIALS AND METHODS: Explorative tympanotomy was performed for the diagnosis, localization and repair of the fistula in the patient who had a pre-diagnosis of perilymphatic fistula. Topical fluorescein was applied intraoperatively to localize the defect. RESULT: A clear change of color was distinguished from yellow to green leading to diagnosis of the perilymphatic fistula and also showed the origin of the fistula. CONCLUSION: Topical application of dilute fluorescein is a convenient and effective tool in the diagnosis and localization of perilymphatic fistula.

Endolymphatic hydrops evaluation on MRI: Practical considerations.

Four-hour delayed three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence after intravenous gadolinium-based contrast agent administration is an optimal magnetic resonance imaging technique to evaluate endolymphatic hydrops in patients with known or suspected Ménière's disease. Nonenhanced endolymphatic space surrounded by enhanced perilymphatic space is evaluated in the cochlea and vestibule separately. In cochlear hydrops, the scala media is enlarged, potentially obliterating the scala vestibuli. In vestibular hydrops, the size of the saccule becomes equal to or larger than that of the utricle; as hydrops progresses, the saccule and utricle become larger and confluent until complete obliteration of the vestibule's perilymphatic space. In patients with a unilateral clinical presentation of Ménière's disease, it is possible to depict the asymmetries of perilymph enhancement, which may be increased on the affected side and reflect a permeability alteration of the blood-perilymph barrier. In addition, endolymphatic hydrops can be observed in the asymptomatic ear of these patients with a unilateral clinical presentation, showing that Ménière's disease tends to undergo bilateral evolution over time.

CT and MRI for the diagnosis of perilymphatic fistula: a study of 17 surgically confirmed patients.

BACKGROUND: We evaluated the usefulness of CT and MRI for the diagnosis of perilymphatic fistula (PLF) of the round (RW) and/or oval (OW) windows, with surgery as gold standard. METHODS: We retrospectively enrolled 17 patients who presented a surgically confirmed PLF of the round (RW) or oval (OW) windows. All patients were imaged by CT + MRI (T2W SSFP without contrast) prior to surgery (= gold standard). Two radiologists, analyzed the RW and OW on the side of the clinical symptoms and sensitivity (Se) + Specificity (Sp) were calculated. RESULTS: Round window fistula was the most frequent (71%). The best sign of PLF on imaging was a fluid filling of the window niches, which had good Se (83-100% for RW, 66-83% for OW) and Sp (60% for RW, 91-100% for OW). Disorientation of the footplate and pneumolabyrinth were also only observed in 50% of OW PLF. CONCLUSION: The combination of CT and MRI is a reliable tool for a fast and accurate diagnosis of round and oval window perilymphatic fistula, with good sensitivity (> 80%). The most common sign of PLF on imaging is the presence of a fluid-filling in the RW (especially if > 2/3 of the RW niche) or in the OW niches on both CT and MRI. A disorientation of the footplate or the presence of a pneumolabyrinth are clearly in favor of an oval window perilymphatic fistula.

Inner ear fluid-attenuated inversion recovery MRI signal intensity in dogs with vestibular disease.

The inner ear contains endolymph and perilymph. The second is comparable and in continuity with the cerebrospinal fluid (CSF) so it is expected to suppress in fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) if normal. Even though inner ear FLAIR abnormalities have been extensively described in humans with inner ear disease, its diagnostic value in dogs is yet to be proven. The goal of this retrospective cohort study was to investigate the diagnostic utility of FLAIR MRI in dogs with vestibular disease. A review of medical records identified 101 dogs that had brain MRI performed because of vestibular signs. Based on the final diagnosis, patients were allocated to three groups: otitis media/interna, idiopathic vestibular disease, and central vestibular disease. Additionally, a control group (n = 73) included dogs with normal MRI and without vestibular signs. Inner ears were delineated using a region of interest, and signal intensity was measured in FLAIR and T2-weighted images. The percentages of suppression in FLAIR were calculated and compared between affected and unaffected sides of each individual and between groups using a general linear mixed model. Correlation between suppression and CSF cell count and protein concentration was assessed. Affected inner ears in dogs with otitis media/interna had decreased suppression in FLAIR compared to the unaffected side (P < .001), and all other groups (P < .01). No significant correlation was detected between CSF results and suppression. These results show the diagnostic value of FLAIR in otitis media/interna due to lack of suppression in the affected inner ear.

Endogenous α1-antitrypsin levels in the perilymphatic fluid correlates with severity of hearing loss.

OBJECTIVES: To determine the levels of endogenous α1-antitrypsin in the perilymph of patients undergoing cochlear implant (CI), and its reverse association with the severity of hearing loss. STUDY DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study includes 38 patients undergoing CI surgery, 11 patients diagnosed with congenital deafness and 27 non-congenital deafness, eight patients diagnosed with moderate hearing loss (N = 8; PTA = 70 dB), severe hearing loss (N = 11; PTA 70-90 dB) and profound hearing loss (N = 19; PTA > 90 dB). MAIN OUTCOME AND MEASURE: 1 to 12 µL perilymphatic fluids were collected by micropipette. α1-antitrypsin levels were determined, and current and historic audiological parameters were obtained. RESULTS: The congenital and non-congenital group exhibited AAT concentrations of 2.5 ± 1.9 × 106 LFQ and 3.2 ± 1.2 × 106 LFQ, respectively (mean ± SD; P = .38). Mean levels of α1-antitrypsin in the perilymph fluid within the moderate group was 3.64 × 106  ± 2.1 × 106 LFQ vs 3.5 × 106  ± 1.2 × 106 in severe hearing loss (P = .81) and 2.4 × 106  ± 1.1 × 106 LFQ in the profound hearings loss group (P = .06). The difference in levels of AAT in samples from the severe hearings loss group vs the profound hearings loss group reached statistical significance (P = .04). CONCLUSION: Insufficiency in α1-antitrypsin levels in the perilymph fluid of the inner ear appears to display a relationship with the severity of hearing loss. The prospect of introducing clinical-grade plasma-purified α1-antitrypsin directly onto the site of cochlear injury deserves thorough investigation.

An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs.

INTRODUCTION: Noise-induced hearing loss (NIHL) is an increasing problem in society and accounts for a third of all cases of acquired hearing loss. NIHL is caused by formation of reactive oxygen species (ROS) in the cochlea causing oxidative stress. Hydrogen gas (H2) can alleviate the damage caused by oxidative stress and can be easily administered through inhalation. OBJECTIVES: To present a protocol for untargeted metabolomics of guinea pig perilymph and investigate the effect of H2 administration on the perilymph metabolome of noise exposed guinea pigs. METHODS: The left ear of guinea pigs were exposed to hazardous impulse noise only (Noise, n = 10), noise and H2 (Noise + H2, n = 10), only H2 (H2, n = 4), or untreated (Control, n = 2). Scala tympani perilymph was sampled from the cochlea of both ears. The polar component of the perilymph metabolome was analyzed using a HILIC-UHPLC-Q-TOF-MS-based untargeted metabolomics protocol. Multivariate data analysis (MVDA) was performed separately for the exposed- and unexposed ear. RESULTS: MVDA allowed separation of groups Noise and Noise + H2 in both the exposed and unexposed ear and yielded 15 metabolites with differentiating relative abundances. Seven were found in both exposed and unexposed ear data and included two osmoprotectants. Eight metabolites were unique to the unexposed ear and included a number of short-chain acylcarnitines. CONCLUSIONS: A HILIC-UHPLC-Q-TOF-MS-based protocol for untargeted metabolomics of perilymph is presented and shown to be fit-for-purpose. We found a clear difference in the perilymph metabolome of noise exposed guinea pigs with and without H2 treatment.

The value of four stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Menière's disease on MRI.

PURPOSE: There is still a clinical-radiologic discrepancy in patients with Menière's disease (MD). Therefore, the purpose of this study was to investigate the reliability of current MRI endolymphatic hydrops (EH) criteria according to Baráth in a larger study population and the clinical utility of new imaging signs such as a supplementary fourth low-grade vestibular EH and the degree of perilymphatic enhancement (PE) in patients with Menière's disease (MD). METHODS: This retrospective study included 148 patients with probable or definite MD according to the 2015 American Academy of Otolaryngology, Head and Neck Surgery criteria who underwent a 4-h delayed intravenous Gd-enhanced 3D-FLAIR MRI between January 2015 and December 2016. Vestibular EH, vestibular PE, cochlear EH, and cochlear PE were reviewed twice by three experienced readers. Cohen's Kappa and multivariate logistic regression were used for analysis. RESULTS: The intra- and inter-reader reliability for the grading of vestibular-cochlear EH and PE was excellent (0.7 < kappa < 0.9). The two most distinctive characteristics to identify MD are cochlear PE and vestibular EH which combined gave a sensitivity and specificity of 79.5 and 93.6%. By addition of a lower grade vestibular EH, the sensitivity improved to 84.6% without losing specificity (92.3%). Cochlear EH nor vestibular PE showed added-value. CONCLUSIONS: MRI using vestibular-cochlear EH and PE grading system is a reliable technique. A four-stage vestibular EH grading system in combination with cochlear PE assessment gives the best diagnostic accuracy to detect MD.

Rat Model of Ménière's Attack: Intratympanic Injection of Potassium Chloride Produces Direction-Changing Spontaneous Nystagmus and Hearing Fluctuations.

The major symptoms of Ménière's disease are episodic vertigo, fluctuating hearing loss, and tinnitus. Direction-changing spontaneous nystagmus is a characteristic vestibular finding in Ménière's disease. In the acute stage, spontaneous nystagmus beating to the affected side (irritative nystagmus) is often observed, while paralytic nystagmus beating to the healthy side is found in the chronic stage. This direction-changing nystagmus can be reproduced in guinea pigs by increasing the potassium ion concentration in the perilymph. The objectives of the present study were to examine the effects of increasing the potassium ion concentration of the rat perilymph on hearing and nystagmus. Under isoflurane anesthesia, 22 rats received intratympanic injection of different concentrations of potassium chloride (KCl) solution or distilled water: groups 1, 2, 3, and 4 received saturated (3.4 M) KCl solution, 2 M KCl, 1 M KCl, and distilled water, respectively. The nystagmus direction and number per 15 s were monitored for 150 min. In the other 8 rats, hearing was monitored 30 min and 20 h after intratympanic injection of 2 M KCl (group 5) or distilled water (group 6) using the auditory brainstem responses. Rats in groups 1 and 2 showed spontaneous irritative nystagmus beating to the affected ear followed by paralytic nystagmus beating to the contralateral side. In group 3, irritative nystagmus occurred but paralytic nystagmus was rarely observed. Rats in group 4 showed no nystagmus. Rats in group 5 showed significant hearing impairment 30 min after KCl injection that recovered 20 h later. Control animals in group 6 showed no significant changes in hearing. The reversible hearing impairment with direction-changing spontaneous nystagmus induced by potassium injection into the tympanic cavity in rats was quite similar to that observed in acute Ménière's attacks. This rat model could be used for basic research investigating the pathophysiological mechanisms underlying Ménière's attacks.

Dexamethasone and Dexamethasone Phosphate Entry into Perilymph Compared for Middle Ear Applications in Guinea Pigs.

Dexamethasone phosphate is widely used for intratympanic therapy in humans. We assessed the pharmacokinetics of dexamethasone entry into perilymph when administered as a dexamethasone phosphate solution or as a micronized dexamethasone suspension, with and without inclusion of poloxamer gel in the medium. After a 1-h application to guinea pigs, 10 independent samples of perilymph were collected from the lateral semicircular canal of each animal, allowing entry at the round window and stapes to be independently assessed. Both forms of dexamethasone entered the perilymph predominantly at the round window (73%), with a lower proportion entering at the stapes (22%). When normalized by applied concentration, dexamethasone phosphate was found to enter perilymph far more slowly than dexamethasone, in accordance with its calculated lipid solubility and polar surface area properties. Dexamethasone phosphate therefore has a problematic combination of kinetic properties when used for local therapy of the ear. It is relatively impermeable and enters perilymph only slowly from the middle ear. It is then metabolized in the ear to dexamethasone, which is more permeable through tissue boundaries and is rapidly lost from perilymph. Understanding the influence of molecular properties on the distribution of drugs in perilymph provides a new level of understanding which may help optimize drug therapies of the ear.

Proteome Analysis of Human Perilymph Using an Intraoperative Sampling Method.

The knowledge about the etiology and pathophysiology of sensorineural hearing loss (SNHL) is still very limited. This study aims at the improvement of understanding different types of SNHL by proteome analysis of human perilymph. Sampling of perilymph was established during inner ear surgeries (cochlear implantation, vestibular schwannoma surgeries), and safety of the sampling method was determined by checking hearing threshold with pure-tone audiometry postoperatively. An in-depth shot-gun proteomics approach was performed to identify cochlear proteins and the individual proteome in perilymph of patients. This method enables the identification and quantification of protein composition of perilymph. The proteome of 41 collected perilymph samples with volumes of 1-12 µL was analyzed by data-dependent acquisition, resulting in overall 878 detected protein groups. At least 203 protein groups were solely identified in perilymph, not in reference samples (serum, cerebrospinal fluid), displaying a specific protein pattern for perilymph. Samples were grouped by patient's age and surgery type, leading to the identification of some proteins specific to particular subgroups. Proteins with different abundances between different sample groups were subjected to classification by gene ontology annotations. The identified proteins might serve as biomarkers to develop tools for noninvasive inner ear diagnostics and to elucidate molecular profiles of SNHL.

Manganese-enhanced MRI (ME MRI) in evaluation of the auditory pathway in an experimental rat model.

This study aimed to explore the optimal dose and manner of administration for visualization of the auditory pathway on manganese-enhanced MRI (ME MRI). Twenty-four healthy male Sprague-Dawley rats were randomly divided into three experimental groups (n = 8 for Groups A, B and C). The rats in Groups A, B and C were subjected to MnCl2 injection through the tympanum, inner ear endolymph and perilymph, respectively (0.2 M for four rats and 0.4 M for the others in each group) and observed at 1, 2, 3, 4, 7 and 10 days after the operation with 3.0 T MRI. The signal intensity (SI) and dynamic changes of the auditory pathways at various times, and at two doses through three injection routes, were compared by statistical analysis. Administration of MnCl2 through the perilymph best showed the complete auditory pathway (P < 0.01), whereas administration though the tympanum only demonstrated part of the pathway. The SI was highest at 24 h after administration of the tracer and began to decline at 48 h. The SI of the auditory cortex was higher after the injection of 0.4 M MnCl2 than that of 0.2 M MnCl2 . ME MRI best demonstrated the whole auditory pathway at 24 h after the injection of 0.4 M MnCl2 through the perilymph in the rat, which provided an optimal method for the study of ME MRI of the auditory pathway in the animal model.

Exploring Inner Ear and Brain Connectivity through Perilymph Sampling for Early Detection of Neurological Diseases: A Provocative Proposal.

Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by performing perilymph sampling. However, current studies have only focused on the diagnosis of such as otologic conditions. Hearing loss is a feature of certain neuroinflammatory disorders such as multiple sclerosis, and sensorineural hearing loss (SNHL) is widely detected in Alzheimer's disease. Although the environment of the inner ear is highly regulated, there are several communication pathways between the perilymph of the inner ear and cerebrospinal fluid (CSF). Thus, examination of the perilymph may help understand the mechanism behind the hearing loss observed in certain neuroinflammatory and neurodegenerative diseases. Herein, we review the constituents of CSF and perilymph, the anatomy of the inner ear and its connection with the brain. Then, we discuss the relevance of perilymph sampling in neurology. Currently, perilymph sampling is only performed during surgical procedures, but we hypothesize a simplified and low-invasive technique that could allow sampling in a clinical setting with the same ease as performing an intratympanic injection under direct visual check. The use of this modified technique could allow for perilymph sampling in people with hearing loss and neuroinflammatory/neurodegenerative disorders and clarify the relationship between these conditions; in fact, by measuring the concentration of neuroinflammatory and/or neurodegenerative biomarkers and those typically expressed in the inner ear in aging SNHL, it could be possible to understand if SNHL is caused by aging or neuroinflammation.

Our Experience with Labyrinthine Fistula: Prospective Hearing Outcomes.

Introduction: Chronic otitis media with cholesteatoma is a locally destructive middle ear infection with bone erosive properties which can lead to fistula if erodes labyrinth. Materials and Methods: A prospective observational study was conducted at tertiary health care centre with a total of 12 patients who presented with complaints of otorrhoea, hearing loss and vertigo. Such patients were evaluated clinic audiologically and radiologically as a pre op assessment. Post-surgery audiological assessment was done. Results: Hearing preservation was seen in 91.7% patients and none of the patients had iatrogenic sensorineural hearing loss. Conclusion: Complete removal of the cholesteatoma is beneficial and does not lead to any iatrogenic SNHL when performed meticulously. A newer way of diagnosing membranous labyrinthine breach utilizing Magnetic Resonance Imaging T2 Diffusion Weighted (MRI- T2 DW) sequence can be implemented.