Cochlear Implantation Outcomes in Patients With Sporadic Inner Ear Schwannomas With and Without Simultaneous Tumor Resection.

OBJECTIVES: Describe a single institution's cochlear implant outcomes for patients with inner ear schwannomas (IES) in the setting of various tumor management strategies (observation, surgical resection, or stereotactic radiosurgery [SRS]). STUDY DESIGN: Single-institution retrospective review. PATIENTS: Patients diagnosed with isolated, sporadic IES who underwent cochlear implantation (CI). INTERVENTIONS: CI with or without IES treatment. MAIN OUTCOME MEASURES: Speech perception outcomes, tumor status. RESULTS: Twelve patients with IES underwent CI with a median audiologic and radiologic follow-up of 12 months. Six patients underwent complete resection of the tumor at the time of CI, four underwent tumor observation, and two underwent SRS before CI. At 1 year after CI for all patients, the median consonant-nucleus-consonant (CNC) word score was 55% (interquartile range, 44-73%), and the median AzBio sentence in quiet score was 77% (interquartile range, 68-93%). Overall, those with surgical resection performed similarly to those with tumor observation (CNC 58 versus 61%; AzBio in quiet 74 versus 91%, respectively). Patients who underwent tumor resection before implantation had a wider range of speech performance outcomes compared with patients who underwent tumor observation. Two patients had SRS treatment before CI (10 months previous and same-day as CI) with CNC word scores of 6 and 40%, respectively. CONCLUSIONS: Patients with IES who underwent CI demonstrated similar speech performance outcomes (CNC 56% and AzBio 82%), when compared with the general cochlear implant population. Patients who underwent either tumor observation or surgical resection performed well after CI.

Intralabyrinthine Schwannoma Mimicking Posterior Canalithiasis.

Intralabyrinthine schwannomas are a rare subgroup of vestibular schwannomas located within the membranous labyrinth of the inner ear and are known for their variable clinical presentations and symptoms. In the present study, we report on a patient with a persistent history of dizziness and positional vertigo, who was misdiagnosed with posterior canalithiasis. As hearing loss was not developed until late in the disease course, the patient was not properly diagnosed until magnetic resonance imaging revealed an intralabyrinthine schwannoma, which was not discovered on earlier imaging. In addition to the unusual clinical presentation, we describe the audio-vestibular profile of our patient. We suggest that a thorough vestibular evaluation, including caloric testing and a careful examination of the inner ear on imaging, is warranted in cases of treatment of refractory vertigo, even in patients where a diagnosis seems certain.

Retrolabyrinthine Bone Thickness as a Radiologic Marker for the Hypoplastic Endotype in Menière Disease.

BACKGROUND AND PURPOSE: Menière disease (MD) manifests in 2 major endotypes: one with a hypoplastic, underdeveloped endolymphatic sac (MD-hp) and the other with a normally developed sac that degenerates over time (MD-dg). Determining the specific endotype in patients is important for predicting disease progression, tailoring patient counseling, and optimizing treatment strategies. Endotype diagnosis involves measuring an angular trajectory of the vestibular aqueduct (ATVA), with an ATVA ≥140° indicative of MD-hp and an ATVA ≤120° of MD-dg. However, assessing the ATVA can be challenging. This study aimed to explore the link between ATVA and the thickness of the retrolabyrinthine bone as an alternative diagnostic measure that could provide differentiation between MD endotypes using CT and MR imaging. MATERIALS AND METHODS: Retrospective review of CT temporal bone imaging from 32 adult patients with definite MD (60 ears) and 33 age-matched controls without MD or other inner ear symptoms (61 ears) was performed. The ATVA and retrolabyrinthine bone thickness were measured using uniform methodology on standardized axial CT images. Comparative analyses were performed to determine the correlation between ATVA and retrolabyrinthine bone thickness. Additionally, from a separate cohort of 11 patients (22 ears), CT and MR examinations of the temporal bone were retrospectively reviewed for retrolabyrinthine bone thickness measurements, to verify the correlation across the 2 modalities. RESULTS: The average retrolabyrinthine bone thickness was statistically significantly different between MD endotypes, being a mean of 0.8 (SD, 0.3) mm in patients with MD-hp (ATVA ≥140°) and 2.0 (SD, 0.9) mm in patients with MD-dg (ATVA ≤120°), with a consistent pattern of thin retrolabyrinthine bone in MD-hp and variable thickness in MD-dg. Receiver operating characteristic curve analysis within the MD cohort revealed that a retrolabyrinthine bone thickness ≥1.2 mm effectively rules out MD-hp. Excellent interrater reliability was noted for the retrolabyrinthine measurement, and there was near-perfect correlation between CT and MR measurements. CONCLUSIONS: Retrolabyrinthine bone thickness proved to be a useful and straightforward alternative marker for distinguishing MD endotypes, being particularly useful for excluding MD-hp. Including information on retrolabyrinthine bone thickness should be considered a routine part of reporting in the context of MD imaging.

Variability in Inner Ear Morphology Among a Family With Pendred Syndrome Due to a SLC26A4 Gene Variant.

OBJECTIVES: Pendred syndrome, an autosomal recessive disorder, is often associated with pathogenic variants of the SLC26A4 gene that encodes the pendrin protein. Given its autosomal recessive inheritance, tracing the family history and screening siblings become crucial once a diagnosis of Pendred syndrome is confirmed. This case report aims to underscore the variability in inner ear morphology within a family diagnosed with Pendred syndrome, all carrying the same SLC26A4 gene mutation. METHODS: A chart review and a review of the literature. RESULTS: We present a family of 4, all of whom possess sensorineural hearing loss due to the same homozygous SLC26A4 variant c.919-2A>G. Intriguingly, clinical manifestations, especially inner ear deformities, displayed variability among family members. Notably, 1 family member exhibited a normal cochleovestibular structure morphology, which was rarely reported in the literature. CONCLUSIONS: This report highlights the significance of genetic testing and familial consultation when a proband exhibits typical Pendred syndrome symptoms. It also underscores that the inner ear morphology can exhibit variability among family members, even with the same homozygous SLC26A4 variant.

Visualization of Reissner's membrane in the mouse inner ear using highly sensitive magnetic resonance imaging analysis.

Although research on hearing loss, including the identification of causative genes, has become increasingly active, the pathogenic mechanism of hearing loss remains unclear. One of the reasons for this is that the structure of the inner ear of mice, which is commonly used as a genetically modified animal model, is too small and complex, making it difficult to accurately capture abnormalities and dynamic changes in vivo. Especially, Reissner's membrane is a very important structure that separates the perilymph and endolymph of the inner ear. This malformation or damage induces abnormalities in hearing and balance. Until now, imaging analyses, such as magnetic resonance imaging (MRI) and computed tomography, are performed to investigate the inner ear structure in vivo; however, it has been difficult to analyze the small inner ear structure of mice owing to resolution. Therefore, there is an urgent need to develop an image analysis method that can accurately capture the structure of the inner ear of mice including Reissner's membrane, both dynamically and statically. This study aimed to investigate whether it is possible to accurately capture the structure (e.g., Reissner's membrane) and abnormalities of the inner ear of mice using an 11.7 T MRI. By combining two types of MRI methods, in vivo and ex vivo, we succeeded for the first time in capturing the fine structure of the normal mouse inner ear, such as the Reissner's membrane, and inflammatory lesions of otitis media mouse models in detail and accurately. In the future, we believe that understanding the state of Reissner's membrane during living conditions will greatly contribute to the development of research on inner ear issues, such as hearing loss.

[Primary central nervous system lymphoma presenting as a unilateral internal auditory canal lesion: a case report].

A 61-year-old man with right hearing loss and staggering for seven months was diagnosed with sudden deafness although previous evaluation with MRI indicated minor abnormal findings. During follow-up, he developed hypogeusia, right facial nerve palsy, pain in right mandible, right-sided temporal pain, and cerebellar ataxia. Cerebrospinal fluid examination at admission revealed reduced glucose concentration and elevated soluble interleukin-2 receptor (sIL-2R) level, whereas serum sIL-2R level was within the normal range. Brain MRI showed a swollen contrast-enhanced lesion extending from the right internal auditory canal to the middle cerebellar peduncle. Gallium-67 (67Ga) single-photon emission-computed tomography-computed tomography (SPECT-CT) revealed abnormal accumulation at the lesion site. Pathologic analysis of the tumor after resection led to the diagnosis of primary central nervous system lymphoma. In the present case, the MRI and 67Ga SPECT-CT characteristics were distinct from those of vestibular schwannoma. In addition, elevation of sIL-2R in the cerebrospinal fluid but not in serum was useful for differential diagnosis.

Unilateral Multifocal Inner Ear and Internal Auditory Canal or Cerebellopontine Angle Cochleovestibular Schwannomas-Genetic Analysis and Management by Surgical Resection and Cochlear Implantation.

OBJECTIVE: To describe the genetic characteristics and the management of two very rare cases of unilateral multifocal inner ear and internal auditory canal or cerebellopontine angle cochleovestibular schwannomas not being associated to full neurofibromatosis type 2-related schwannomatosis. PATIENTS: In a 29-year-old man and a 55-year-old woman with single-sided deafness multifocal unilateral cochleovestibular schwannomas were surgically resected, and hearing was rehabilitated with a cochlear implant (CI). Unaffected tissue was analyzed using next generation sequencing of the NF2 gene. Tumor tissue was analyzed using a 340-parallel sequencing gene panel. MAIN OUTCOME MEASURES: Mutations in the NF2 gene, word recognition score for monosyllables at 65 dB SPL (WRS 65 ) with CI. RESULTS: No disease-causing mutation was detected in the examined sequences in blood leucokytes. All tumor samples revealed, among others, somatic pathogenic NF2 mutations. While the anatomically separate tumors in case 1 were likely molecular identical, the tumors in case 2 showed different genetic patterns. WRS 65 was 55% at 6 years of follow-up and 60% at 4.5 years of follow-up, respectively. CONCLUSIONS: The occurrence of multifocal unilateral cochleovestibular schwannomas without pathogenic variants in NF2 in non-affected blood leucocytes can be associated with mosaic NF2 -related schwannomatosis (case 1), or with likely sporadic mutations (case 2) and may be overlooked due to their extreme rarity. Although challenging, successful hearing rehabilitation could be achieved through surgical resection of the tumors and cochlear implantation.

Langerhans cell histiocytosis involving the temporal bone with destruction and subsequent reossification of the bony labyrinth boundaries.

PURPOSE: With an incidence between 1-9/100 000 per year, Langerhans cell histiocytosis (LCH) is a rather rare disease from the hemato-oncologic disease spectrum (Hayes et al. 2009). The tumorlike disease with proliferation of histiocytic cells may manifest as localized to one organ or disseminated with infiltration of a wide variety of organs. Approximately 25-30 % of these cases show involvement of the temporal bone (Ni et al. 2017). CASE DESCRIPTION: With vertigo persisting for three years, chronic mastoiditis, and acute progressive hearing loss bilaterally (r > l) for three weeks, a 41-year-old woman presented at an emergency department. The DVT showed extensive bony destruction of large parts of the temporal bone on both sides, involving the vestibular organ, the cochlea, and the internal auditory canal. To confirm the suspicion of a systemic inflammatory process, a PE was performed from the mastoid with bioptic confirmation of an LCH. Systemic therapy was initiated. Post-therapeutic imaging showed almost complete remission with reossification of the preexisting defect zones and the internal auditory canal and labyrinth structures again showed bony margins. Clinically, there was an improvement of the vegetative symptoms with remaining bilateral sensorineural hearing loss. DISCUSSION: LCH of the temporal bone is a rare and often misdiagnosed disease due to its nonspecific clinical presentation. Awareness of temporal bone LCH and its occurrence in adults is essential for accurate and consistent diagnosis. KEY POINTS: · LCH is a rather rare disease from the hemato-oncological spectrum. · Affection of the temporal bone, especially such an extensive one (as in this case report), is rather atypical in adulthood. · Use of systemic therapy resulted in remission. · There was complete reossification of the osseous structures post-therapy. · A cochlear implant was able to be implanted to compensate for hearing loss.

Patterns of Signal Intensity in CISS MRI of the Inner Ear and Eye.

BACKGROUND: Constructive interference in steady state (CISS) is a gradient echo magnetic resonance imaging (MRI) pulse sequence that provides excellent contrast between cerebrospinal fluid and adjacent structures but is prone to banding artifacts due to magnetic field inhomogeneities. We aimed to characterize artifacts in the inner ear and eye. METHODS: In 30 patients (60 ears/eyes) undergoing CISS sequence MRI, nine low-signal intensity regions were identified in the inner ear and compared to temporal bone histopathology. The number and angle of bands across the eye were examined. RESULTS: In the cochlea, all ears had regions of low signal corresponding to anatomy (modiolus (all), spiral lamina (n = 59, 98.3%), and interscalar septa (n = 50, 83.3%)). In the labyrinth, the lateral semicircular canal crista (n = 42, 70%) and utricular macula (n = 47, 78.3%) were seen. Areas of low signal in the vestibule seen in all ears may represent the walls of the membranous utricle. Zero to three banding artifacts were seen in both eyes (right: 96.7%, mean 1.5; left: 93.3%, mean 1.3). CONCLUSION: Low signal regions in the inner ear on CISS sequences are common and have consistent patterns; most in the inner ear represent anatomy, appearing blurred due to partial volume averaging. Banding artifacts in the eye are more variable.

The Breakdown of Blood-Labyrinth Barrier Makes it Easier for Drugs to Enter the Inner Ear.

PURPOSE: This study aimed to investigate dynamic change of permeability of blood-labyrinth barrier (BLB) after noise exposure and its effect on the drug delivery efficiency of systemic administration. METHODS: Gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (DEX) were used as tracers, and magnetic resonance imaging (MRI) and immunofluorescence were used to observe the change of the BLB after strong noise exposure in guinea pigs. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to observe the effect of the breakdown of BLB after noise exposure on the drug delivery efficiency of intravenous DEX. The guinea pigs were divided into 6 groups: normal group (N), 1, 3, 5, 8, and 12 days after noise exposure groups (P1, P3, P5, P8, P12), with 5 animals in each group. RESULTS: The BLB changes dynamically after noise exposure. Increased permeability of the blood-endolymph barrier, the endolymph-perilymph barrier, and the blood-nerve barrier was observed at days 1-3, 1-5, and 1-8, respectively, after noise exposure in guinea pigs. Higher drug concentration in the cochlear tissue was obtained by intravenous administration of DEX in guinea pigs during the time window of increased permeability of the BLB. CONCLUSION: After noise exposure, the increased BLB permeability makes it easier for drugs to enter the inner ear from blood. In guinea pigs, 1-8 days after strong noise exposure, the drug delivery efficiency of systemic administration increased. After 8 days, the efficiency gradually returned to normal level. 1-8 days after noise exposure may be the best intervention time for systemic administration. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2377-2386, 2024.

Cerebellopontine angle tumor presenting as acute audiovestibular syndrome.

BACKGROUND: Acute audiovestibular deficits may be a harbinger of vestibular schwannoma (VS). OBJECTIVE: To investigate clinical and laboratory features of 25 consecutive patients with VS presenting with acute audiovestibular deficits. METHODS: A symptomatic combination of acute audiovestibular deficits was investigated. Audiometric and vestibular function tests, and internal auditory canal magnetic resonance imaging (IAC MRI) results were evaluated. RESULTS: Varying combinations of symptoms may develop in VS patients with acute audiovestibular deficits, of whom sudden hearing loss (HL) without acute vertigo or acute facial nerve palsy (FNP) was most common. The most common audiometric configuration was high-tone hearing loss, and no patient showed low-tone hearing loss. IAC MRI demonstrated that the tumor had an intracanalicular portion and attachment to the bony IAC wall in all patients and widened the IAC wall in some patients. CONCLUSION: Different symptomatic combinations of acute audiovestibular deficits may develop in patients with VS. Awareness about the possibility of VS as a cause of sudden HL, acute vertigo, and acute FNP, as well as subsequent IAC MRI scanning is vital to earlier diagnosis of VS in these patients.

Enhanced Cochlear Transduction by AAV9 with High-Concentration Sucrose.

The inner ear is a primary lesion in sensorineural hearing loss and has been a target in gene therapy. The efficacy of gene therapy depends on achieving sufficient levels of transduction at a safe vector dose. Vectors derived from various adeno-associated viruses (AAVs) are predominantly used to deliver therapeutic genes to inner ear cells. AAV9 and its variants vector are attractive candidates for clinical applications since they can cross the mesothelial cell layer and transduce inner hair cells (IHCs), although this requires relatively high doses. In this study, we investigated the effects of sucrose on the transduction of a variant of the AAV9 vector for gene transfer in the inner ear. We found that high concentrations of sucrose increased gene transduction in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in vitro. In addition, we demonstrated that simultaneous administration of sucrose enhanced the transduction of mouse IHCs and spiral ligament cells using an AAV9 variant vector. The procedure did not increase the thresholds in the auditory brainstem response, suggesting that sucrose had no adverse effect on auditory function. This versatile method may be valuable in the development of novel gene therapies for adult-onset sensorineural hearing loss.

Imaging Guide to Inner Ear Malformations: An Illustrative Review.

Inner ear malformation (IEM) with associated sensoryneural hearing loss (SNHL) is a major cause of childhood disability. Computed tomography (CT) and magnetic resonance imaging (MRI) imaging play important and often complementary roles in diagnosing underlying structural abnormalities and surgical planning allows for direct visualization of the cochlear nerve and is the preferred imaging modality prior to cochlear implantation. CT is helpful to assess osseous anatomy and when evaluating children with mixed hearing loss or syndromic associations. When reviewing these cases, it is important for the radiologist to be familiar with the key imaging features. In this article, we will present the imaging findings associated with different inner ear malformations associated with congenital sensorineural hearing loss.

MRI surveillance after translabyrinthine vestibular schwannoma resection and cochlear implantation: is it feasible?

PURPOSE: Cochlear implantation in patients with vestibular schwannomas is of increasing importance and interest. Two remaining challenges are the assessment of conduction of the cochlear nerve and the possibility of postoperative surveillance with magnetic resonance imaging. The aim of the current study was to assess follow-up imaging and determine the visibility of the internal auditory canal after vestibular schwannoma resection and cochlear implantation as well as in patients with persistent vestibular schwannomas and cochlear implants in place. Visibility of the internal auditory canal, cerebellopontine angle, and labyrinth were evaluated and graded. METHODS: For this retrospective study, 15 MR examinations of 13 patients after translabyrinthine vestibular schwannoma resection and ipsilateral cochlear implantation were included. All patients had been implanted with an MED-EL cochlear implant. Magnetic resonance imaging was carried out on a 1.5T device. All patients were prepped according to the manufacturer's recommendations. RESULTS: All 15 examinations were carried out without any adverse event during imaging, such as pain, magnet dislocation, or malfunction. The internal auditory canal and the cerebellopontine angle were sufficiently visible in all cases to allow for vestibular schwannoma follow-up. CONCLUSION: Magnetic resonance imaging surveillance of the internal auditory canal following vestibular schwannoma resection and cochlear implantation is feasible and safe with modern implants with a 1.5T magnetic resonance imaging device using metal artifact reduction sequences. Necessary follow-up imaging should not be a contraindication for cochlear implantation in patients with vestibular schwannomas.

Delivery of gene therapy through a cerebrospinal fluid conduit to rescue hearing in adult mice.

Inner ear gene therapy has recently effectively restored hearing in neonatal mice, but it is complicated in adulthood by the structural inaccessibility of the cochlea, which is embedded within the temporal bone. Alternative delivery routes may advance auditory research and also prove useful when translated to humans with progressive genetic-mediated hearing loss. Cerebrospinal fluid flow via the glymphatic system is emerging as a new approach for brain-wide drug delivery in rodents as well as humans. The cerebrospinal fluid and the fluid of the inner ear are connected via a bony channel called the cochlear aqueduct, but previous studies have not explored the possibility of delivering gene therapy via the cerebrospinal fluid to restore hearing in adult deaf mice. Here, we showed that the cochlear aqueduct in mice exhibits lymphatic-like characteristics. In vivo time-lapse magnetic resonance imaging, computed tomography, and optical fluorescence microscopy showed that large-particle tracers injected into the cerebrospinal fluid reached the inner ear by dispersive transport via the cochlear aqueduct in adult mice. A single intracisternal injection of adeno-associated virus carrying solute carrier family 17, member 8 (Slc17A8), which encodes vesicular glutamate transporter-3 (VGLUT3), rescued hearing in adult deaf Slc17A8-/- mice by restoring VGLUT3 protein expression in inner hair cells, with minimal ectopic expression in the brain and none in the liver. Our findings demonstrate that cerebrospinal fluid transport comprises an accessible route for gene delivery to the adult inner ear and may represent an important step toward using gene therapy to restore hearing in humans.

Dual inhibition of the endothelin and angiotensin receptor ameliorates renal and inner ear pathologies in Alport mice.

Alport syndrome (AS), a type IV collagen disorder, leads to glomerular disease and, in some patients, hearing loss. AS is treated with inhibitors of the renin-angiotensin system; however, a need exists for novel therapies, especially those addressing both major pathologies. Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist (DEARA) under clinical development for focal segmental glomerulosclerosis and IgA nephropathy. We report the ability of sparsentan to ameliorate both renal and inner ear pathologies in an autosomal-recessive Alport mouse model. Sparsentan significantly delayed onset of glomerulosclerosis, interstitial fibrosis, proteinuria, and glomerular filtration rate decline. Sparsentan attenuated glomerular basement membrane defects, blunted mesangial filopodial invasion into the glomerular capillaries, increased lifespan more than losartan, and lessened changes in profibrotic/pro-inflammatory gene pathways in both the glomerular and the renal cortical compartments. Notably, treatment with sparsentan, but not losartan, prevented accumulation of extracellular matrix in the strial capillary basement membranes in the inner ear and reduced susceptibility to hearing loss. Improvements in lifespan and in renal and strial pathology were observed even when sparsentan was initiated after development of renal pathologies. These findings suggest that sparsentan may address both renal and hearing pathologies in Alport syndrome patients. © 2023 Travere Therapeutics, Inc and The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Transcanal Transpromontorial Approaches to the Internal Auditory Canal: A Systematic Review.

OBJECTIVE: Exclusive endoscopic (EETTA) and expanded (ExpTTA) transcanal transpromontorial approaches have shown promising results for treating internal auditory canal (IAC) lesions. We reviewed the literature to answer the question: "Do EETTA and ExpTTA achieve high rates of complete resection and low rates of complications in treating patients with IAC pathologies?" DATA SOURCES: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched. REVIEW METHODS: Studies reporting EETTA/ExpTTA for IAC pathologies were included. Indications and techniques were discussed and meta-analyzed rates of outcomes and complications were obtained with random-effect model meta-analyses. RESULTS: We included 16 studies comprising 173 patients, all with non-serviceable hearing. Baseline FN function was mostly House-Brackmann-I (96.5%; 95% CI: 94.9-98.1%). Most lesions were vestibular/cochlear schwannomas (98.3%; 95% CI: 96.7-99.8%) of Koos-I (45.9%; 95% CI: 41.3-50.3%) or II (47.1%; 95% CI: 43-51.1%). EETTA was performed in 101 patients (58.4%; 95% CI: 52.4-64.3%) and ExpTTA in 72 (41.6%; 95% CI: 35.6-47.6%), achieving gross-total resection in all cases. Transient complications occurred in 30 patients (17.3%; 95% CI: 13.9-20.5%), with meta-analyzed rates of 9% (95% CI: 4-15%), comprising FN palsy with spontaneous resolution (10.4%; 95% CI: 7.7-13.1%). Persistent complications occurred in 34 patients (19.6%; 95% CI: 17.1-22.2%), with meta-analyzed rates of 12% (95% CI: 7-19%), comprising persistent FN palsy in 22 patients (12.7%; 95% CI: 10.2-15.2%). Mean follow-up was 16 months (range, 1-69; 95% CI: 14.7-17.4). Post-surgery FN function was stable in 131 patients (75.8%; 95% CI: 72.1-79.5%), worsened in 38 (21.9%; 95% CI: 18.8-25%), and improved in 4 (2.3%; 95% CI: 0.7-3.9%), with meta-analyzed rates of improved/stable response of 84% (95% CI: 76-90%). CONCLUSION: Transpromontorial approaches offer newer routes for IAC surgery, but their restricted indications and unfavorable FN outcomes currently limit their use. Laryngoscope, 133:2856-2867, 2023.

The Future of Vestibular Schwannoma Management.

The future of the management of both sporadic and neurofibromatosis type 2-asscoiated vestibular schwannomas (VSs) will be shaped by cutting-edge technologic and biomedical advances to enable personalized, precision medicine. This scoping review envisions the future by highlighting the most promising developments published, ongoing, planned, or potential that are relevant for VS, including integrated omics approaches, artificial intelligence algorithms, biomarkers, liquid biopsy of the inner ear, digital medicine, inner ear endomicroscopy, targeted molecular imaging, patient-specific stem cell-derived models, ultra-high dose rate radiotherapy, optical imaging-guided microsurgery, high-throughput development of targeted therapeutics, novel immunotherapeutic strategies, tumor vaccines, and gene therapy.

Comparing Linear and Volumetric Tumor Measurements During Observation of Growing Sporadic Vestibular Schwannomas.

OBJECTIVE: To assess the correlation between linear and volumetric changes in vestibular schwannomas (VS). STUDY DESIGN: Retrospective imaging review was performed on patients diagnosed with sporadic VS from 2000 to 2019 who demonstrated linear growth on observation with serial magnetic resonance imaging (MRI). SETTING: Two large tertiary care centers. METHODS: Changes in diameter on serial MRI scans, measured by 1995 American Academy of Otolaryngology-Head and Neck Surgery guidelines, were compared to changes in volume, calculated by segmentation. RESULTS: Ninety-two patients had VS confined to the internal auditory canal (IAC) with 236 MRIs analyzed, and 108 patients had VS involving the cerebellopontine angle (CPA) with 193 MRIs analyzed. The Spearman rank correlation coefficients between changes in diameter and volume for IAC and CPA tumors were 0.43 (p < .001) and 0.65 (p < .001), respectively. Linear diameter increases of 1 to <2 mm corresponded to a median volume change of 32% (interquartile range [IQR]: 6%-86%) for IAC tumors, compared to 23% (IQR: 13%-40%) for CPA tumors. Linear diameter increases of 2 to <3 mm (ie, the minimum linear diameter change classically considered "true growth") corresponded to a median volume change of 42% (IQR: 23%-100%) and 47% (IQR: 26%-69%) for IAC and CPA tumors, respectively. CONCLUSION: Changes in linear diameter significantly correlated with changes in volume for IAC and CPA tumors, although diameter changes that did not meet the definition of linear growth (<2 mm) had corresponding median volume changes in excess of 20% for both IAC and CPA tumors.

Oridonin employs interleukin 1 receptor type 2 to treat noise-induced hearing loss by blocking inner ear inflammation.

NOD-like receptor protein 3 (NLRP3) inflammasomes trigger the inflammatory cascades and participate in various inflammatory diseases, including noise-induced hearing loss (NIHL) caused by oxidative stress. Recently, the anti-inflammatory traditional medicine oridonin (Ori) has been reported to provide hearing protection in mice after noise exposure by blocking the NLRP3-never in mitosis gene A-related kinase 7 (NEK7)-inflammasome complex assembly. Using RNA sequencing analysis, we further elucidated that interleukin 1 receptor type 2 (IL1R2) may be another crucial factor regulated by Ori to protect NIHL. We observed that IL1R2 expression was localized in spiral ganglion neurons, inner and outer hair cells, in Ori-treated mouse cochleae. Additionally, we confirmed that ectopic overexpression of IL1R2 in the inner ears of healthy mice using an adeno-associated virus delivery system significantly reduced noise-induced ribbon synapse lesions and hearing loss by blocking the "cytokine storm" in the inner ear. This study provides a novel theoretical foundation for guiding the clinical treatment of NIHL.