Cases historically presumed to be perilymphatic fistula of the round and/or oval window may be cases of third window syndrome due to inner ear dehiscence. Perilymphatic fistula (PLF) is a condition where a pathologic external connection of the perilymphatic space is present, often with an associated otic capsule or stapes defect. Recently, it has become evident that otic capsule defects in locations that lack perilymphatic fluid leak can cause clinical symptoms. Such clinical entities are deemed "third window" syndromes-among which superior semicircular canal dehiscence is the most common. Human temporal bone specimens underwent histopathologic study of cases previously suspected to have PLF at the oval or round window. These specimens were further scrutinized for the presence of an alternate site of inner ear dehiscence that may have potentially caused a third window syndrome. Thirty-one out of 34 of the cases (61 ears) from a previously published study on PLF were reviewed. Altogether, dehiscences were noted at the following locations: cochlea-facial (11), superior semicircular canal (5), endolymphatic sac-jugular bulb (4), cochlea-internal auditory canal (3), posterior semicircular canal (2), and an enlarged/patent cochlear aqueduct (2). One patient with a histologic dehiscence had an audiogram consistent with third window syndrome. The findings suggest that many clinical cases historically presumed to be PLF of the round and/or oval window may, in fact, be cases of third window syndrome due to inner ear dehiscence with pathology at sites other than the oval or round windows.

Technical advancements in inner ear MRI promise improved diagnosis and management of Ménière disease (MD), but a key challenge in optimizing 3D-FLAIR protocols for inner ear imaging lies in selecting the optimal flip angle. This study evaluates the 3 most common flip angle parameters used in 3D-FLAIR imaging for MD through a prospective, head-to-head comparison of image quality at constant flip angle (CFA) 120°, CFA 140°, and variable flip angle (VFA) obtained 4 hours after IV administration of a single-dose gadolinium-based contrast agent. We prospectively enrolled 16 consecutive patients at our institution's otology clinic on the basis of the 2015 American Academy of Otolaryngology-Head and Neck Surgery criteria for MD, including acute or fluctuating symptoms of vertigo, hearing loss, tinnitus, or aural fullness. Each patient underwent delayed inner ear MRI at 3T with the 3 most commonly used flip angles: CFA 120°, CFA 140°, and VFA. The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were determined for each flip angle. Assessment of blood-labyrinthine barrier (BLB) permeability, utricle-saccule discrimination, and endolymphatic hydrops (EH) was performed by 2 head and neck neuroradiologists. Thirty-one ears were analyzed. One ear was excluded on the basis of a prior history of left labyrinthectomy after failed medical management of MD. There were 17 symptomatic and 14 asymptomatic ears determined by clinical and hearing evaluation. The SNR of the perilymphatic space and CNR of the endolymphatic space were significantly higher at CFA 140°, followed by CFA 120°, and then VFA (P < .05). There was significantly improved visualization of EH, the utricle-saccule complex, and BLB permeability at CFA 140° (P < .05), with excellent interobserver agreement (κ > 0.80). Our study demonstrates that 3D-FLAIR inner ear imaging using CFA 140° and single-dose IV gadolinium contrast at 3T is a reliable method for detecting EH.

Cross-channel feature transfer 3D U-Net for automatic segmentation of the perilymph and endolymph fluid spaces in hydrops MRI.

Optical coherence tomography imaging demonstrates endolymphatic hydrops in the lateral and posterior semicircular canals in noise-exposed mice.

A recently proposed non-contrast MRI technique for evaluating endolymphatic hydrops employs inversion recovery without T2-preparation and the subtraction of 2 inversion time images. However, our high-resolution non-contrast positive endolymph images (PEI) reveal inconsistencies in delineating the endolymphatic space, challenging this method’s reliability. Comprehensive analysis is required to address the interplay among signal intensity, T1 relaxation times, and inversion efficiency within endolymphatic and perilymphatic spaces to establish its diagnostic accuracy.

Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea. We sought to assess PSCC infusion of gold NPs into the cochlea, including the NPs' distribution and effect on cochlear mechanics. We performed optical coherence tomography (OCT) imaging to monitor PSCC infusion of gold NPs into the cochlear chambers. OCT imaging demonstrated that the infusion specifically targeted the perilymphatic spaces within the cochlea. We assessed cochlear mechanics by using OCT vibrometry to measure sound-evoked movements of the basilar membrane. We found no changes in cochlear mechanics between measurements at baseline, after the PSCC canalostomy, immediately after the infusion, and 1 h after the infusion of gold NPs (p > 0.05, paired t-test). These findings validate the PSCC infusion approach for perfusing the cochlear perilymphatic space with a nanoparticle delivery system. Thus, PSCC infusion of nanoparticles is a feasible therapeutic delivery technique for treating inner ear disorders while preserving residual cochlear function.

Effective, reproducible, and safe delivery of therapeutics into the inner ear is required for the prevention and treatment of hearing loss. A commonly used delivery method is via the posterior semicircular canal (PSCC); however, its specific targeting within the cochlea remains unclear, impacting precision and reproducibility. To assess safety and target specificity, we conducted in vivo recordings of the pharmacological manipulations delivered through the PSCC. Measurements of auditory brainstem response (ABR), vibrometry, and vestibular behavioral and sensory-evoked potential (VsEP) revealed preserved hearing and vestibular functions after artificial perilymph injections. Injection of curare, a mechanoelectrical transducer (MET) channel blocker that affects hearing when in the endolymph, had no effect on ABR or VsEP thresholds. Conversely, injection of CNQX, an AMPA receptor blocker, or lidocaine, a Na+ channel blocker, which affects hearing when in the perilymph, significantly increased both thresholds, indicating that PSCC injections selectively target the perilymphatic space. In vivo tracking of gold nanoparticles confirmed their exclusive distribution in the perilymph during PSCC injection, supporting the pharmacological finding. Together, PSCC injection is a safe method for inner ear delivery, specifically targeting the perilymphatic space. Our findings will allow for precise delivery of therapeutics within the inner ear for therapeutic and research purposes.

Determining the concentration of prestin in human blood, cerebrospinal fluid (CSF), and perilymph (PL), and evaluating its suitability as a clinical biomarker for sensori-neural hearing loss (SNHL). Human blood, CSF, and PL samples were intraoperatively collected from 42 patients with tumors of the internal auditory canal or with intracochlear tumors undergoing translabyrinthine or middle fossa tumor removal. Prestin concentration was measured using enzyme-linked immunosorbent assay and linear regression analyses were performed to investigate its associations with audiological as well as vestibular test results. Tertiary referral center. The median prestin concentration in blood samples of the 42 study participants (26 women, mean ± standard deviation age, 52.7 ± 12.5 years) was 1.32 (interquartile range, IQR, 0.71-1.99) ng/mL. CSF prestin levels were significantly higher with 4.73 (IQR, 2.45-14.03) ng/mL (P = .005). With 84.74 (IQR, 38.95-122.00) ng/mL, PL prestin concentration was significantly higher compared to blood (P = .01) and CSF (P = .03) levels. Linear regression analyses showed significant associations of CSF prestin concentration with preoperative hearing levels (pure-tone average and word recognition; P = .008, R2 = 0.1894; P = .03, R2 = 0.1857), but no correlations with blood or PL levels. This study's findings highlight the volatile nature of prestin levels and provide the first insights into this potential biomarker's concentrations in body fluids apart from blood. Future investigations should comprehensively assess human prestin levels with different etiologies of SNHL, prestin's natural homeostasis and systemic circulation, and its temporal dynamics after cochlear trauma. Finally, clinically approved detection kits for prestin are urgently required prior to considering a potential translational implementation of this diagnostic technique.

This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.

Possible causes of vertigo attacks in Meniere’s disease

Temporal bone (TB) fractures are frequently accompanied by intracranial injury. This study aimed to analyze combined intracranial injuries in relation to functional changes in the inner ear, including those of the contralateral ear, in patients with TB fractures. Ninety-four patients (mean age: 35.6 ± 18.7 years, M : F=67 : 27) diagnosed with unilateral TB fracture were included. Bone conduction (BC) threshold, word recognition score (WRS), and changes in vestibular function were compared based on intracranial injuries, focusing on the contralateral side. Various types of intracranial injuries were observed (67.9%). Among these, a significant association between traumatic brain injury (TBI) and otic capsule-violating fractures was noted. The BC threshold on the fractured side significantly deteriorated in patients with TBI. Additionally, a significantly worse BC threshold was confirmed on the contralateral side in patients with TBI, intracranial hemorrhage (ICH), and contrecoup injury. The follow-up BC threshold did not improve or differ, regardless of high-dose steroid administration. The initial WRS and canal paresis in the bithermal caloric test were not significantly different in the presence of each intracranial injury. Concurrent fluctuations in the pressure of the cerebrospinal fluid space and perilymphatic space were speculated to be the potential underlying mechanisms. A significantly worse BC threshold was confirmed on the contralateral side of patients with TBI, contrecoup injury, ICH, and on fracture sides of patients with TBI.

Cochlear aqueduct revisited: A histological study using human fetuses

Blood-labyrinthine barrier leakage has been reported in sudden sensorineural hearing loss (SSNHL). We compared immediate post-contrast 3D heavily T2-weighted fluid-attenuated inversion recovery (FLAIR), T1 spin echo (SE), and 3D T1 gradient echo (GRE) sequences, and heavily T2-weighted FLAIR (hvT2F) with and without deep learning-based reconstruction (DLR) in detecting perilymphatic enhancement. Fifty-four patients with unilateral SSNHL who underwent ear MRI with three sequences were included. We compared asymmetry scores, confidence scores, and detection rates of perilymphatic enhancement among the three sequences and obtained 3D hvT2F with DLR from 35 patients. The above parameters and subjective image quality between 3D hvT2F with and without DLR were compared. Asymmetry scores and detection rate of 3D hvT2F were significantly higher than 3D GRE T1 and SE T1 (respectively, 1.37, 0.11, 0.19; p < 0.001). Asymmetry scores significantly increased with DLR compared to 3D hvT2F for experienced and inexperienced readers (respectively, 1.77 vs. 1.40, p = 0.036; 1.49 vs. 1.03, p = 0.012). The detection rate significantly increased only for the latter (57.1% vs. 31.4%, p = 0.022). Patients with perilymphatic enhancement had significantly higher air conduction thresholds on initial (77.96 vs. 57.79, p = 0.002) and 5days after presentation (63.38 vs. 41.85, p = 0.019). 3D hvT2F significantly increased the detectability of perilymphatic enhancement compared to 3D GRE T1 and SE T1. DLR further improved the conspicuity of perilymphatic enhancement in 3D hvT2F. 3D hvT2F and DLR are useful for evaluating blood-labyrinthine barrier leakage; furthermore, they might provide prognostic value in the early post-treatment period. Ten-minute post-contrast 3D heavily T2-weighed FLAIR imaging is a potentially efficacious sequence in demonstrating perilymphatic enhancement in patients with sudden sensorineural hearing loss and may be further improved by deep learning-based reconstruction. • 3D heavily T2-weighted FLAIR (3D hvT2F) is a sequence sensitive in detecting low concentrations of contrast in the perilymphatic space. • 3D hvT2F sequences properly demonstrated perilymphatic enhancement in sudden sensorineural hearing loss compared to T1 sequences and were further improved by deep learning-based reconstruction (DLR). • 3D hvT2F and DLR are efficacious sequences in detecting blood-labyrinthine barrier leakage and with potential prognostic information.

Spontaneous intracranial hypotension (SIH) is a rare condition characterized by orthostatic headache, pulsatile tinnitus, vertigo, nausea, and fluctuating hearing loss; this latter seems to be due to the development of cochlear endolymphatic hydrops following negative cerebrospinal fluid (CSF) pressure transmitted to the perilymphatic space through a patent cochlear aqueduct. We here describe a case of bilateral progressive sensorineural hearing loss (SNHL) due to intracranial hypotension caused by an undiagnosed spontaneous CSF leak from a skull base defect in a middle-aged woman. To the best of our knowledge, this is the first report describing a SNHL in a patient affected by SIH secondary to sphenoidal CSF leak.

Our aim in this study was to characterize the morphology of the endolymphatic compartment on histopathology in individuals with Ménière's disease (MD) and to determine why hydrops of the saccule is more pronounced than that of other compartments of the inner ear in MD. Temporal bones from 9 patients with idiopathic MD and from 10 individuals without MD/endolymphatic hydrops were examined. The inner ear fluid compartments in normal ears, and ears with MD were three-dimensionally reconstructed and their volume was calculated. The thickness of the membranes of the labyrinth was measured, and both ruptures of the membranes and patency of the utriculoendolymphatic (UEV; Bast's) valve were assessed. In ears with MD, the saccule and the cochlear duct were most frequently hydropic; the utricle was involved approximately half as frequently. In ears without MD, the Reissner's membrane and the membranous wall of the saccule were thinner than that of the utricle and of the lateral semicircular canal ( p < 0.01). The lateral semicircular canal did not show signs of hydrops. In all ears with MD in which the utricle exceeded the average volume of normals (6 of 12), the UEV was open or there was a rupture in the utricle. Increases in endolymphatic pressure may cause a primary swelling of the apical cochlear duct and saccule, both of which have relatively thin membranes. Hydrops in the utricle may occur less frequently because of a thicker wall, because of a functioning UEV, and when the saccule has already occupied most of the vestibular perilymphatic space.

Characteristic findings in the human fetus vestibule: A human temporal bone study

Transient connection between the vestibular aqueduct and utricle: A study using sagittal sections of human embryonic heads

Delayed post-gadolinium magnetic resonance imaging (MRI) detects changes of endolymphatic hydrops (EH) within the inner ear in Meniere's disease (MD). A systematic review with meta-analysis was conducted to summarise the diagnostic performance of MRI descriptors across the range of MD clinical classifications. Case-controlled studies documenting the diagnostic performance of MRI descriptors in distinguishing MD ears from asymptomatic ears or ears with other audio-vestibular conditions were identified (MEDLINE, EMBASE, Web of Science, Scopus databases: updated 17/2/2022). Methodological quality was evaluated with Quality Assessment of Diagnostic Accuracy Studies version 2. Results were pooled using a bivariate random-effects model for evaluation of sensitivity, specificity and diagnostic odds ratio (DOR). Meta-regression evaluated sources of heterogeneity, and subgroup analysis for individual clinical classifications was performed. The meta-analysis included 66 unique studies and 3073 ears with MD (mean age 40.2-67.2years), evaluating 11 MRI descriptors. The combination of increased perilymphatic enhancement (PLE) and EH (3 studies, 122 MD ears) achieved the highest sensitivity (87% (95% CI: 79.92%)) whilst maintaining high specificity (91% (95% CI: 85.95%)). The diagnostic performance of "high grade cochlear EH" and "any EH" descriptors did not significantly differ between monosymptomatic cochlear MD and the latest reference standard for definite MD (p = 0.3; p = 0.09). Potential sources of bias were case-controlled design, unblinded observers and variable reference standard, whilst differing MRI techniques introduced heterogeneity. The combination of increased PLE and EH optimised sensitivity and specificity for MD, whilst some MRI descriptors also performed well in diagnosing monosymptomatic cochlear MD. • A meta-analysis of delayed post-gadolinium magnetic resonance imaging (MRI) for the diagnosis of Meniere's disease is reported for the first time and comprised 66 studies (3073 ears). • Increased enhancement of the perilymphatic space of the inner ear is shown to be a key MRI feature for the diagnosis of Meniere's disease. • MRI diagnosis of Meniere's disease can be usefully applied across a range of clinical classifications including patients with cochlear symptoms alone.

The detection rate of premortem MR imaging endolymphatic hydrops is lower than that of postmortem endolymphatic hydrops in Ménière disease, indicating that current MR imaging techniques may underestimate endolymphatic hydrops. Therefore, we prospectively investigated whether a novel high-resolution MR imaging technique, the 3D zoomed imaging technique with parallel transmission real inversion-recovery (3D-ZOOMit real IR), would improve the detection of endolymphatic hydrops compared with conventional 3D TSE inversion-recovery with real reconstruction. Fifty patients with definite unilateral Ménière disease were enrolled and underwent 3D-ZOOMit real IR and 3D TSE inversion-recovery with real reconstruction 6 hours after IV gadolinium injection. The endo- and perilymph spaces were scored separately. The contrast-to-noise ratio, SNR, and signal intensity ratio of the 2 sequences were respectively calculated and compared. The presence of endolymphatic hydrops was evaluated. The endolymphatic space in the cochlea and vestibule was better visualized with 3D-ZOOMit real IR than with conventional 3D TSE inversion-recovery with real reconstruction (P < .001). There were differences between the 2 sequences in the evaluation of no cochlear hydrops and cochlear hydrops (both, P < .017). All contrast-to-noise ratio, SNR, and signal intensity ratio values of 3D-ZOOMit real IR images were statistically higher than those of conventional 3D TSE inversion-recovery with real reconstruction (all, P < .001). The 3D-ZOOMit real IR sequences are superior to conventional 3D TSE inversion-recovery with real reconstruction sequences in visualizing the endolymphatic space, detecting endolymphatic hydrops, and discovering contrast permeability.

Symptoms: Dizziness and Deafness