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There is growing interest in research on segmentation for the vestibular schwannoma (VS) and cochlea using high-resolution T2 (hrT2) imaging over contrast-enhanced T1 (ceT1) imaging due to the contrast agent side effects. However, the hrT2 imaging remains a problem of insufficient annotated data, which is fatal for building more robust segmentation models. To address the issue, recent studies have adopted unsupervised domain adaptation approaches that translate ceT1 images to hrT2 images. However, previous studies did not consider the size and visual characteristics of the target objects, such as VS and cochlea, during image translation. Specifically, those works simply performed normalization on the entire image without considering its significant impact on the quality of the translated images. These approaches tend to erase the small target objects, making it difficult to preserve the structure of these objects when generating pseudo-target images. Furthermore, they may also struggle to accurately reflect the unique style of the target objects within the images. Therefore, we propose a target-aware unsupervised domain adaptation framework, designed for translating target objects, each tailored to their unique visual characteristics and size using target-aware normalization. We demonstrate the superiority of the proposed framework on a publicly available challenge dataset. Codes are available at https://github.com/Bokyeong-Kang/TANQ ., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Both vestibular schwannoma (VS) and Meniere's disease (MD) patients underwent hydrops MRI to clarify the relationship between VS and endolymphatic hydrops (EH)., Methods: Eighty patients with VS or MD underwent an inner ear test battery followed by hydrops MRI, and were then divided into 3 groups. Group A comprised 58 MD patients (62 ears) with positive EH but negative VS. Group B included 18 VS patients (18 ears) with negative EH, while Group C consisted of 4 patients (4 ears) who had VS concomitant with EH. Another 14 MD patients who tested negative for EH on hydrops MRI were initially excluded from this cohort, but were later included for comparison., Results: The decreasing prevalence of EH at the cochlea, saccule and utricle in Group A was identified in 59 (95%), 42 (68%) and 40 (65%) ears, respectively, mimicking a declining sequence of abnormality rates running from audiometry (86%), cervical vestibular-evoked myogenic potential (cVEMP) test (55%) to the ocular (oVEMP) test (53%). However, such decreasing trend was not identified in Groups B and C. In Groups C and A combined, 4 (6%) of 62 EH patients had concomitant VS. Conversely, 4 (18%) of 22 VS patients in Groups C and B combined had concurrent EH., Conclusion: A very low (6%) rate of VS in EH patients indicates that VS in EH patients may be coincidental. In contrast, EH was identified in 18% prevalence of VS patients, mirroring the 22% prevalence of cochlear EH demonstrated in VS donors through histopathological studies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Purpose: For patients with vestibular schwannomas (VS), a conservative observational approach is increasingly used. Therefore, the need for accurate and reliable volumetric tumor monitoring is important. Currently, a volumetric cutoff of 20% increase in tumor volume is widely used to define tumor growth in VS. The study investigates the tumor volume dependency on the limits of agreement (LoA) for volumetric measurements of VS by means of an inter-observer study., Methods: This retrospective study included 100 VS patients who underwent contrast-enhanced T1-weighted MRI. Five observers volumetrically annotated the images. Observer agreement and reliability was measured using the LoA, estimated using the limits of agreement with the mean (LOAM) method, and the intraclass correlation coefficient (ICC)., Results: The 100 patients had a median average tumor volume of 903 mm 3 (IQR: 193-3101). Patients were divided into four volumetric size categories based on tumor volume quartile. The smallest tumor volume quartile showed a LOAM relative to the mean of 26.8% (95% CI: 23.7-33.6), whereas for the largest tumor volume quartile this figure was found to be 7.3% (95% CI: 6.5-9.7) and when excluding peritumoral cysts: 4.8% (95% CI: 4.2-6.2)., Conclusion: Agreement limits within volumetric annotation of VS are affected by tumor volume, since the LoA improves with increasing tumor volume. As a result, for tumors larger than 200 mm 3 , growth can reliably be detected at an earlier stage, compared to the currently widely used cutoff of 20%. However, for very small tumors, growth should be assessed with higher agreement limits than previously thought., (© 2024. The Author(s).)

Cancer-associated fibroblast (CAF) composition within the same organ varies across different cancer subtypes. Distinct CAF subtypes exhibit unique features due to interactions with immune cells and the tumor microenvironment. However, data on CAF subtypes in individuals with vestibular schwannoma (VS) are lacking. Therefore, we aimed to distinguish CAF subtypes at the single-cell level, investigate how stem-like CAF characteristics influence the tumor immune microenvironment, and identify CAF subtype-specific metabolic reprogramming pathways that contribute to tumor development. Data were analyzed from three patients with VS, encompassing 33,081 single cells, one bulk transcriptome cohort, and The Cancer Genome Atlas Pan-Cancer database (RNA sequencing and clinical data). Our findings revealed that antigen-presenting CAFs are linked to substantially heightened immune activity, supported by metabolic reprogramming, which differs from tumorigenesis. High expression of the stem-like CAF gene signature correlated with poor prognosis in low-grade gliomas within the pan-cancer database. This is the first study to classify CAF subtypes in VS patients and identify a therapeutic vulnerability biomarker by developing a stem-like CAF gene signature. Personalized treatments tailored to individual patients show promise in advancing precision medicine.

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., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Neurofibromatosis type 2 (NF2) is a rare disorder that causes vestibular schwannomas (VS), meningiomas and ependymomas. To date, there is no FDA approved drug-based treatment for NF2. We have previously identified that BET inhibition can selectively reduce growth of the NF2-null schwannoma and Schwann cells in vitro and tumorigenesis in vivo and, separately, reported that inhibition of Focal Adhesion Kinase 1 (FAK1) via crizotinib has antiproliferative effects in NF2-null Schwann cells. The current study was aimed at determining whether combined BET and FAK inhibition can synergize and to identify the mechanisms of action. A panel of normal and NF2-null Schwann and schwannoma cell lines were used to characterize the effects of combined BET and FAK inhibition in vitro and in vivo using pharmacological and genetic approaches. The mechanism of action was explored by chromatin immunoprecipitation, ChIP-PCR, western blotting, and functional approaches. We find that combined BET and FAK inhibition are synergistic and inhibit the proliferation of NF2-null schwannoma and Schwann cell lines in vitro and in vivo, by arresting cells in the G1/S and G2/M phases of the cell cycle. Further, we identify the mechanism of action through the downregulation of FAK1 transcription by BET inhibition, which potentiates inhibition of FAK by 100-fold. Our findings suggest that combined targeting of BET and FAK1 may offer a potential therapeutic option for the treatment of NF2-related schwannomas., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To report the natural history of vestibular schwannoma (VS) who elected an initial period of observation and identify prognostic factors. To describe the natural history of growing VS, identify prognostic factors, and review the most recent literature., Study Design: Prospective cohort study and literature review., Setting: Tertiary referral center., Patients: Adult patients diagnosed with a VS between January 1998 and February 2023., Intervention: Magnetic resonance imaging surveillance., Main Outcome Measures: Growth-free survival and subsequent growth-free survival considering significant growth as a change in size of ≥2 mm., Results: Of 430 patients undergoing observation with serial magnetic resonance imaging, 193 (44.9%) demonstrated significant growth at a median of 1.6 years (interquartile range, 0.94-3.51). Of the 193 patients who presented an initial episode of growth, 137 elected to continue to be observed. Of those, 83 (60.6%) presented a second episode of growth at a median of 1.43 years (interquartile range, 1.00-2.49). The subsequent growth-free survival rates (95% confidence interval) at 1, 3, 5, 7, and 10 years were 91.79% (87.26-96.56%), 64.44% (56.56-73.42%), 52.52% (44.23-62.35%), 42.23% (33.92-52.56%), and 36.11% (27.89-46.76%), respectively. Univariate and multivariate Cox regression analyses showed that EC tumor location and initial growth rate were significant predictors of subsequent growth., Conclusions: Close observation after documentation of growth is an appropriate management in well-selected cases given that only around 56% of the tumor will continue to grow. Extracanalicular tumor location and initial growth rate are promising prognostic factors to help determine which patient would be a better candidate for close surveillance after initial documentation of growth., Competing Interests: Sources of support and disclosure of funding: B.J.P.—stock ownership: Cochlear, medical consultancy; Sanofi and Merck, Sharp & Dohme. The remaining authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Background: A schwannoma is a nerve sheath tumor that is formed by Schwann cells. Vestibular schwannomas are thought to account for the majority of intracranial schwannomas. Nonvestibular schwannomas account for about 10%, about half of which are trigeminal schwannomas. Multiple intracranial schwannomas originating from different cranial nerves are extremely rare., Methods: We describe the clinical case of a 42-year-old female patient with vestibular schwannoma and multiple trigeminal schwannomas., Results: That case shows how multiple trigeminal schwannomas were identified intraoperatively during elective surgery for vestibular schwannoma removal, most of which were resected. No new neurological deficits were observed in the patient., Conclusions: The presence of multiple intracranial schwannomas is extremely rare in neurosurgical practice and can change the intraoperative strategy and the course of the surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate tumor control and facial nerve outcomes after gross-total (GTR), near-total (NTR), and subtotal resection (STR) of sporadic vestibular schwannomas (VS)., Data Sources: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were searched in August 2021 through inception following PRISMA guidelines., Review Methods: English language articles reporting tumor control and facial nerve outcomes of adults (≥18 years) with NTR and STR of VS were evaluated. Study characteristics, demographics data, tumor characteristics, type of surgical intervention, and outcome measures on tumor control and facial nerve function were collected. Pooled relative risk (RR) estimates for tumor recurrence and facial nerve outcomes were calculated and stratified by extent of resection., Results: From an initial search of 2504 articles, 48 studies were included in the analysis. When comparing 1108 patients who underwent NTR to 3349 patients with GTR, the pooled RR of recurrence in the NTR cohort was 2.94 (95% confidence interval [CI] 1.65-5.24, P = .0002). When comparing 1016 patients who underwent STR to 6171 patients with GTR, the pooled RR of recurrence in the STR cohort was 11.50 (95% CI 6.64-19.92, P < .0001). Estimates for risk of tumor regrowth for less-than-complete resection are presented. There was no elevated risk of adverse facial nerve outcome (defined as House-Brackmann grade III and above) in each category of extent of resection compared to GTR., Conclusion: Extent of resection predicts risk of tumor recurrence/regrowth following microsurgical resection. Favorable facial nerve outcome should be weighed against the increased risk of regrowth and the potential need for further treatment., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Purpose: Limited data provides guidance on the management of vestibular schwannomas (VSs) that have progressed despite primary Gamma Knife radiosurgery (GKRS). The present article reports our long-term experience after repeat GKRS for VS with sustained progression after solely primary GKRS management., Methods: A retrospective review of 1997 patients managed between 1987 and 2023 was conducted. Eighteen patients had sustained tumor progression after primary GKRS and underwent repeat GKRS. The median repeat GKRS margin dose was 11 Gy (IQR: 11-12), the median tumor volume was 2.0 cc (IQR: 1.3-6.3), and the median cochlear dose in patients with preserved hearing was 3.9 Gy (IQR: 3-4.1). The median time between initial and repeat GKRS was 65 months (IQR: 38-118)., Results: The median follow-up was 70 months (IQR: 23-101). After repeat GKRS, two patients had further tumor progression at 4 and 21 months and required partial resection of their tumors. The 10-year actuarial tumor control rate after repeat GKRS was 88%. Facial nerve function was preserved in 13 patients who had House-Brackmann grade 1 or 2 function at the time of repeat GKRS. Two patients with serviceable hearing preservation (Gardner-Robertson grade 1 or 2) at repeat GKRS retained that function afterwards. In patients with tinnitus, vestibular dysfunction, and trigeminal neuropathy, symptoms remained stable or improved for 16/16 patients, 12/15 patients, and 10/12 patients, respectively. One patient developed facial twitching in the absence of tumor growth 21 months after repeat GKRS., Conclusions: Repeat GKRS effectively controlled tumor growth and preserved cranial nerve outcomes in most patients whose VS had sustained progression after initial primary radiosurgery., (© 2024. The Author(s).)

Purpose: It has been shown that in large vestibular schwannomas (VS), radiosurgery (SRS) is inferior with respect to tumor control compared to microsurgical resection (SURGERY). However, SURGERY poses a significantly higher risk of facial-function deterioration (FFD). The aim of this study was to illustrate the effectiveness in terms of number-needed-to-treat/operate (NNO), number-needed-to-harm (NNH), and likelihood-of-harm/help (LHH) by comparing both treatment modalities in large VS., Methods: This was a retrospective, dual-center cohort study. Tumor size was classified by Hannover Classification. Absolute risk reduction and risk increase were used to derive additional estimates of treatment effectiveness, namely NNO and NNH. LHH was then calculated by a quotient of NNH/NNO to illustrate the risk-benefit-ratio of SURGERY., Results: Four hundred and forty-nine patients treated met the inclusion criteria. The incidence of tumor recurrence was significantly higher in SRS (14%), compared to SURGERY (3%) resulting in ARR of 11% and NNO of 10. At the same time, SURGERY was related to a significant risk of FFD resulting in an NNH of 12. Overall, the LHH calculated at 1.20 was favored SURGERY, especially in patients under the age of 40 years (LHH = 2.40), cystic VS (LHH = 4.33), and Hannover T3a (LHH = 1.83) and T3b (LHH = 1.80)., Conclusions: Due to a poorer response of large VS to SRS, SURGERY is superior with respect to tumor control. One tumor recurrence can be prevented, when 10 patients are treated by SURGERY instead of SRS. Thus, LHH portrays the benefit of SURGERY in large VS even when taking raised FFD into account., (© 2024. The Author(s).)

Objective: To assess growth rates of residual vestibular schwannoma after subtotal and near-total surgical resection and establishing staging system for risk of residual tumor growth., Study Design: Retrospective cohort study., Setting: Tertiary referral center., Patients: Patients with residual vestibular schwannoma after surgical resection from 2011 to 2023 identified on postoperative MRI defined as near-total resection (NTR, less than 5 mm of remaining tumor), subtotal resection (STR; 5-10 mm) and debulking (>10 mm)., Main Outcome Measures: Tumor growth of 2 mm or more after subtotal or near-total surgical resection of vestibular schwannoma., Results: A total of 56 patients (54% female; mean, standard deviation [SD] age 51 [17] yr) had residual tumor. Mean preoperative tumor size was 3.0 (1.1) cm, and residual tumors involved both sides with similar frequency (right: 52%). Quantitatively, 29% were NTR, 32% were STR, and 39% were debulking. With an average follow-up of 27 (SD 31) months, tumor growth occurred in 11 (20%), tumor shrinkage occurred in 16 (29%), and tumors were unchanged in 29 (51%) cases. Growing residual tumors were treated with radiation (7 patients) or a second surgical resection (4 patients). Multivariable analysis identified lower patient age, larger preoperative tumor size, and larger residual tumor size in risk of residual growth. A residual VS tumor staging system (Age, Tumor, Residual [ATR]) is proposed with most tumors in stage II (22, 42%) or stage III (23, 44%), whereas 7 (14%) tumors are stage I., Conclusions: Approximately 80% of residual VS are stable or shrink in size. Initial observation is advocated after incomplete resection and long-term follow up is needed. Patient age less than 55 years, larger preoperative tumor size, and larger postoperative residual tumor size appear predictive of residual tumor growth.Level of Evidence: 4., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Objective: To evaluate the long-term changes in sporadic vestibular schwannoma (VS) disease-specific quality-of-life (QOL) outcomes., Study Design: Prospective longitudinal study using the Penn Acoustic Neuroma Quality of Life (PANQOL) Scale., Setting: National survey., Patients: Patients with sporadic VS who completed a baseline survey before treatment and at least one follow-up survey recruited through the authors' center and through the Acoustic Neuroma Association., Interventions: Observation, microsurgery, radiosurgery., Main Outcome Measures: Changes in PANQOL scores from baseline to most recent survey., Results: Among 445 eligible patients the mean duration of follow-up was 4.4 (SD, 2.3) years, including 122, 218, and 105 in the observation, microsurgery, and radiosurgery groups, respectively. Patients managed with observation ( p = 0.03) or microsurgery ( p < 0.001) demonstrated improvement in anxiety scores. Changes in facial function scores differed significantly by management group ( p = 0.01), with patients undergoing microsurgery demonstrating a mean decline of 10 points in facial function scores compared with mean declines of 3 for those managed with observation or radiosurgery. Hearing loss scores decreased similarly over time for all three groups ( p = 0.3). There were minimal changes in total PANQOL scores over time across all management groups ( p = 0.5)., Conclusions: Long-term changes in total QOL among VS management groups are not significantly different. Microsurgery may continue to confer an advantage regarding improvement in anxiety postoperatively, but with a greater decline in facial function when compared to observation or radiosurgery. Long-term declines in hearing loss scores were not statistically significantly different among groups., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Background: Elderly patients with vestibular schwannoma (VS) are commonly observed., Object: Retrospective analysis of 25 patients aging ≥ 70 operated on in our neurosurgical department for unilateral VS. The purpose of our study is to propose an algorithm for the treatment of VS in elderly patients., Methods: American Society of Anesthesiology (ASA) Grade I-II patients and Grade III with life-threatening tumors were enrolled. Karnofsky Performance Status Scale (KPS) was used for evalutation of the quality of life. The House-Brackmann (HB) scale for facial nerve (FN) outcome was used. Tumor size was categorized according to Koos' classification. A retrosigmoid approach was used in all cases, except one in which a translabyrinthine approach was performed. Surgical removal graduation: total (GTR), near total (NTR > 95%), subtotal (STR > 90%). The clinical and radiological follow-up period was set first at six months and then at one year after surgery. FN results evaluation was performed at one year, categorized according to House-Brackmann grades I-VI., Results: Mean age: 74,4 years (70-83); 28% ASA I, 56% ASA II, 16% ASA III. Mean tumor size: 2,7 cm (1,5-4,2 cm)., Gtr/ntr: 68%, STR 32%. Mortality was zero. At last follow-up (one year after surgery) FN results were: HBI 81%, HBII 9.5%, HBIII 9.5%; HB IV 0%. Only 4 patients had preoperative HB IV, of whom one improved from HB IV to HB III. Transient complications occurred only in large VS. Re-growth of residue after STR was observed in 3 cases, treated with SRS in 2 cases and observed in 1., Conclusions: An algorithm of treatment of vestibular schwannoma in the elderly is proposed. In particular, in patients in general good conditions, age does not appear to be a major contraindication for microsurgery of VS. FN results at last follow-up are satisfactory and the complication rates are acceptable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To determine the natural history of hearing loss and tumor volume in patients with untreated neurofibromatosis type 2 (NF2)-related schwannomatosis. Moreover, we statistically examined the factors affecting hearing prognosis., Methods: This retrospective cohort study was conducted on 37 ears of 24 patients with NF2-related vestibular schwannomatosis followed up without treatment for more than 1 year. We obtained detailed chronological changes in the PTA and tumor volume in each case over time, and the rate of change per year was obtained. Multivariate analysis was also conducted to investigate factors associated with changes in hearing., Results: The average follow-up period was approximately 9 years, and hearing deteriorated at an average rate of approximately 4 dB/year. The rate of maintaining effective hearing decreased from 30 ears (81%) at the first visit to 19 ears (51%) at the final follow-up. The average rate of change in tumor growth for volume was approximately 686.0 mm 3 /year. This study revealed that most patients with NF2 experienced deterioration in hearing acuity and tumor growth during the natural course. A correlation was observed between an increase in tumor volume and hearing loss (r = 0.686; p < 0.001)., Conclusions: Although the hearing preservation rate in NF2 cases is poor with the current treatment methods, many cases exist in which hearing acuity deteriorates, even during the natural course. Patients with an increased tumor volume during the follow-up period were more likely to experience hearing deterioration. Trial registration number 20140242 (date of registration: 27 October 2014)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Vestibular schwannomas (VSs) are benign tumors often monitored over time, with measurement techniques for assessing growth rates subject to significant interobserver variability. Automatic segmentation of these tumors could provide a more reliable and efficient for tracking their progression, especially given the irregular shape and growth patterns of VS., Methods: Various studies and segmentation techniques employing different Convolutional Neural Network architectures and models, such as U-Net and convolutional-attention transformer segmentation, were analyzed. Models were evaluated based on their performance across diverse datasets, and challenges, including domain shift and data sharing, were scrutinized., Results: Automatic segmentation methods offer a promising alternative to conventional measurement techniques, offering potential benefits in precision and efficiency. However, these methods are not without challenges, notably the "domain shift" that occurs when models trained on specific datasets underperform when applied to different datasets. Techniques such as domain adaptation, domain generalization, and data diversity were discussed as potential solutions., Conclusions: Accurate measurement of VS growth is a complex process, with volumetric analysis currently appearing more reliable than linear measurements. Automatic segmentation, despite its challenges, offers a promising avenue for future investigation. Robust well-generalized models could potentially improve the efficiency of tracking tumor growth, thereby augmenting clinical decision-making. Further work needs to be done to develop more robust models, address the domain shift, and enable secure data sharing for wider applicability., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study aimed to determine if hypointense cochlear magnetic resonance imaging (MRI) constructive interference in steady-state (CISS) signal correlates with hearing outcomes in conservatively managed vestibular schwannoma (VS) patients., Study Design: Retrospective review of 657 cases from 1992 to 2020., Setting: Tertiary academic referral center., Patients: A retrospective review was performed to identify conservatively managed VS patients with appropriate baseline MRI, audiology, and at least 12-month audiological follow-up. Patients were excluded if they progressed to surgery or radiotherapy in less than 12 months, bilateral tumors, or surgery on the contralateral ear., Intervention: Conservatively managed patients with CISS imaging studies and audiology testing., Main Outcome Measures: Primary outcome measure change in pure-tone average (PTA) and word recognition score (WRS). Secondary outcome measures tumor size, presence of lateral fluid cap, or cystic changes., Results: A total of 92 individuals (47% male, 58 ± 11.6 yr) met the inclusion criteria, with 36 (39%) of patients demonstrating abnormal cochlear CISS signal. At baseline, abnormal cochlear CISS signal was associated with higher intracanalicular (IC) length (7.9 versus 6.6 mm, p = 0.0177) and lower WRS (55.7 versus 78.8 dBHL, p = 0.0054). During follow-up, individuals with abnormal cochlear CISS signal had significantly higher PTA (62.4 versus 46.4 dBHL, p = 0.0010). After adjusting for baseline covariates, abnormal cochlear CISS signal was consistently associated with a greater increase in PTA of 8.3 dBHL (95% confidence interval, 2.9-13.7; p = 0.0032) from baseline when compared with the normal group., Conclusions: Abnormal cochlear signal on MRI CISS sequences is associated with poorer hearing outcomes in conservatively managed VS patients., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Objectives: Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis., Methods: We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM)., Results: Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors ("first hit") but distinct "second hit" NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis., Conclusions: Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: To evaluate the predictive factors of tumor growth in patients with vestibular schwannoma (VS) managed with the wait-and-scan approach., Methods: The data of 31 patients diagnosed with intracanalicular VS and followed for > 5 years were retrospectively analyzed. VS was diagnosed according to MRI findings and tumor growth was monitored. Tumor growth was defined as an increase of 2 mm or more in the maximal tumor diameter. The association between the initial tumor size and shape and tumor growth was assessed., Results: Tumor growth was observed in 16 of 31 patients (51.6%) over a mean follow-up duration of 7.3 years. The initial tumor size was not statistically correlated with tumor growth. However, fusiform or cylindrical tumors exhibited higher growth rates than oval or round tumors. Additionally, a significant correlation was observed between cerebellopontine angle extension and tumor shape., Conclusion: In this study, 51.6% of the patients with intracanalicular VS who were managed with the wait-and-scan strategy over a follow-up period of > 5 years showed tumor growth. Tumor shape, especially fusiform or cylindrical shape, was found to be a significant predictor of tumor growth., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Preoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. Besides the preoperative tumor size there are other factors that influence the preoperative hearing function that are frequently discussed. A comprehensive analysis of a large cohort of vestibular schwannomas has the potential to describe new insights and influence the preoperative management. We analyzed clinical factors, imaging data and the expression of the proliferation marker MIB1 as potential influencing factors on the preoperative hearing function in a retrospective cohort of 523 primary sporadic vestibular schwannomas. The results of the preoperative audiometry were quantified using the Gardner-Robertson Score. Uni- and multivariate analyses were performed. Serviceable hearing (Gardner-Robertson class 1 or 2) was documented in 391 patients (74.8%). Factors associated with non-serviceable hearing (Gardner-Robertson class 3-5) were patients of older age (p < 0.0001), larger preoperative tumor volume (p = 0.0013) and widening of the internal acoustic meatus compared to the healthy side (p = 0.0353). Gender and differences in the expression of the proliferation marker MIB1 had no influence on preoperative hearing. In the multivariate nominal logistic regression older age (OR 27.60 (CI 9.17-87.18), p < 0.0001), larger preoperative tumor volume (OR 20.20 (CI 3.43-128.58), p = 0.0011) and widening of the internal acoustic canal (OR 7.86 (CI 1.77-35.46), p = 0.0079) remained independent factors associated with non-serviceable hearing. Widening of the internal acoustic canal is an independent factor for non-serviceable preoperative hearing in vestibular schwannoma patients together with older age and larger preoperative tumor volume., (© 2024. The Author(s).)

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear., (© 2024. The Author(s).)

Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings., Methods: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69). Ethnicity, insurance, maximum tumor size, audiometry, initial treatment recommendation, treatment received, and follow up were recorded and statistical analysis performed to determine differences., Results: Average age at diagnosis (51.7 ± 13.6 TAMC vs 52.3 ± 12.4 PSNH) and gender (58.4% TAMC vs 52.2% PSNH female) were similar. Patients' insurance (TAMC 75.9% privately insured vs PSNH 82% Medicaid) and racial/ethnic profiles (TAMC 67.7% White and 10.0% Hispanic/Latinx, vs PSNH 4.8% White but 59.7% Hispanic/Latinx) were significantly different. Tumor size was larger at PSNH (20.2 ± 13.3 mm) than TAMC (16.6 ± 10.0 mm). Hearing was more impaired at PSNH than TAMC (mean pure tone average 58.3 dB vs 43.9 dB, word recognition scores 52.3% vs 68.2%, respectively). Initial treatment recommendations and treatment received may include more than 1 modality. TAMC patients were offered 66.7% surgery, 31.2% observation, and 5.2% radiation, while PSNH patients offered 50.7% observation, 49.3% surgery, and 8.7% radiation. TAMC patients received 62.9% surgery, 32.5% observation, and 5.3% radiation, while PSNH patients received 36.2% surgery, 59.4% observation, and 14.5% radiation. Follow up and treatment at the same facility was not significantly different between hospitals., Conclusions: Hearing was worse and tumor size larger in patients presenting to PSNH. Despite worse hearing status and larger tumor size, the majority of PSNH patients were initially offered observation, compared to TAMC where most patients were initially offered surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hearing loss is a common side effect of many tumor treatments. However, hearing loss can also occur as a direct result of certain tumors of the nervous system, the most common of which are the vestibular schwannomas (VS). These tumors arise from Schwann cells of the vestibulocochlear nerve and their main cause is the loss of function of NF2, with 95 % of cases being sporadic and 5 % being part of the rare neurofibromatosis type 2 (NF2)-related Schwannomatosis. Genetic variations in NF2 do not fully explain the clinical heterogeneity of VS, and interactions between Schwann cells and their microenvironment appear to be critical for tumor development. Preclinical in vitro and in vivo models of VS are needed to develop prognostic biomarkers and targeted therapies. In addition to VS, other tumors can affect hearing. Meningiomas and other masses in the cerebellopontine angle can compress the vestibulocochlear nerve due to their anatomic proximity. Gliomas can disrupt several neurological functions, including hearing; in fact, glioblastoma multiforme, the most aggressive subtype, may exhibit early symptoms of auditory alterations. Besides, treatments for high-grade tumors, including chemotherapy or radiotherapy, as well as incomplete resections, can induce long-term auditory dysfunction. Because hearing loss can have an irreversible and dramatic impact on quality of life, it should be considered in the clinical management plan of patients with tumors, and monitored throughout the course of the disease., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Disclosure: This study was sponsored only by intramural funding. The institution of the main author receives grants from the following companies: MED-EL Innsbruck, Austria and Cochlear, Sydney, Australia, and AudioCure Pharma GmbH, Berlin, Germany. Other than that, the authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background: Vestibular schwannomas (VSs) remain a challenge due to their anatomical location and propensity to growth. Macrophages are present in VS but their roles in VS pathogenesis remains unknown., Objectives: The objective was to assess phenotypic and functional profile of macrophages in VS with single-cell RNA sequencing (scRNAseq)., Methods: scRNAseq was carried out in three VS samples to examine characteristics of macrophages in the tumour. RT-qPCR was carried out on 10 VS samples for CD14, CD68 and CD163 and a panel of macrophage-associated molecules., Results: scRNAseq revealed macrophages to be a major constituent of VS microenvironment with three distinct subclusters based on gene expression. The subclusters were also defined by expression of CD163, CD68 and IL-1β. AREG and PLAUR were expressed in the CD68+CD163+IL-1β+ subcluster, PLCG2 and NCKAP5 were expressed in CD68+CD163+IL-1β- subcluster and AUTS2 and SPP1 were expressed in the CD68+CD163-IL-1β+ subcluster. RT-qPCR showed expression of several macrophage markers in VS of which CD14, ALOX15, Interleukin-1β, INHBA and Colony Stimulating Factor-1R were found to have a high correlation with tumour volume., Conclusions: Macrophages form an important component of VS stroma. scRNAseq reveals three distinct subsets of macrophages in the VS tissue which may have differing roles in the pathogenesis of VS., (© 2024. The Author(s).)

Background: The expanded transpromontorial transcanal approach (ExpTTA) represents a recent addition to the surgical approaches available for the treatment of vestibular schwannoma. An initial purely endoscopic version has been complemented by the use of the microscope and it is now one of the possible surgical options for small to medium-sized vestibular schwannomas with a predominantly intracanalar development., Methods: This is a series of 54 patients who underwent microsurgical resection of sporadic, unilateral vestibular schwannoma, mainly Koos I-II with non-serviceable hearing, between January 2016 and January 2023 using the expanded transcanal transpromontorial approach. We describe the surgical technique, focusing on anatomical landmarks, and analyzing its advantages and shortcomings. Retrospective analysis of clinical outcomes is presented, including early and late complications. The mean follow-up was 46.7 months., Results: We achieved gross total resection of the lesion in all cases, confirmed on the first follow-up MRI at least 6 months after each procedure. We did not record any intraoperative complication nor disease recurrence. We recorded two postoperative severe facial nerve palsies, one of which was permanent. No cases of disabling vertigo or imbalance were reported, and all patients reported full recovery of autonomy in daily activities. Three cases of otoliquorrhea were managed conservatively successfully., Conclusions: The transcanal transpromontorial approach combines the advantages of endoscopy with the possibilities provided by microsurgery. Our experience confirms its safety in terms of surgical complications and facial nerve outcome. This approach is amongst the treatment options for small-medium schwannomas in patients with impaired hearing, especially in young patients, ensuring radical resection, disease control, and minimal morbidity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Our goal was to develop a 3D tumor slice model, replicating the individual tumor microenvironment and for individual pharmaceutical testing in vestibular schwannomas with and without relation to NF2., Methods: Tissue samples from 16 VS patients (14 sporadic, 2 NF2-related) were prospectively analyzed. Slices of 350 µm thickness were cultured in vitro, and the 3D tumor slice model underwent thorough evaluation for culturing time, microenvironment characteristics, morphology, apoptosis, and proliferation rates. Common drugs - Lapatinib (10 µM), Nilotinib (20 µM), and Bevacizumab (10 µg/ml) - known for their responses in VS were used for treatment. Treatment responses were assessed using CC3 as an apoptosis marker and Ki67 as a proliferation marker. Standard 2D cell culture models of the same tumors served as controls., Results: The 3D tumor slice model accurately mimicked VS ex vivo, maintaining stability for three months. Cell count within the model was approximately tenfold higher than in standard cell culture, and the tumor microenvironment remained stable for 46 days. Pharmacological testing was feasible for up to three weeks, revealing interindividual differences in treatment response to Lapatinib and intraindividual variability in response to Lapatinib and Nilotinib. The observed effects were less pronounced in tumor slices than in standard cell culture, indicating the model's proximity to in vivo tumor biology and enhanced realism. Bevacizumab had limited impact in both models., Conclusion: This study introduces a 3D tumor slice model for sporadic and NF2-related VS, demonstrating stability for up to 3 months, replication of the schwannoma microenvironment, and utility for individualized pharmacological testing., Competing Interests: Declaration of Competing Interest Nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Cerebellopontine angle (CPA) tumors are a common cause of secondary trigeminal neuralgia (TN), characterized by their concealed location, slow progression, and difficulty in early detection. This study aims to explore the clinicopathological characteristics of patients with secondary TN due to CPA tumors to enhance understanding and management of secondary TN., Methods: A retrospective analysis was conducted on clinical data and pathological results of 116 patients with CPA tumor-related TN treated at Xiangya Hospital of Central South University from January 1, 2017 to December 31, 2022. The study analyzed the relationship of tumor pathological types with clinical manifestations, tumor location, surgical methods, and treatment outcomes., Results: Among the cases, 95.7% (111/116) were benign tumors, 3.4% (4/116) were malignant tumors, and 0.9% (1/116) were borderline tumors. Benign tumors were predominantly acoustic neuromas, meningiomas, and schwannomas. Among the patients, 46.6% (54/116) presented with isolated TN, while 53.4% (62/116) exhibited other associated symptoms depending on factors such as tumor growth location and rate. The complete resection rate in this group was over 90%, with 41.4% (48/116) of patients undergoing concurrent microvascular decompression after tumor resection, predominantly for schwannomas. The overall effective rate of surgical treatment reached 93.9%, with schwannomas showing higher efficacy rates compared with acoustic neuromas and meningiomas ( P <0.05). The recurrence rate of acoustic neuromas was significantly higher than that of meningiomas and schwannomas ( P <0.05)., Conclusions: CPA tumors are a major cause of secondary TN, predominantly benign, with occasional underdiagnosed malignant tumors. Early diagnosis and treatment significantly impact prognosis. Different tumor types vary in clinical symptoms, surgical approaches, and treatment efficacy. Surgical strategies should balance tumor resection extent and neural function preservation, with microvascular decompression as necessary.

Background: Gamma Knife Radiosurgery (GKRS) has established a role in treating various benign brain pathologies. The radiosurgery planning necessitates a proper understanding of radiation dose distribution in relation to the target lesion and surrounding eloquent area. The quality of a radiosurgery plan is determined by various planning parameters. Here, we have reviewed various GKRS planning parameters and analyzed their correlation with the morphology of treated brain lesions., Method: A total of 430 treatment plans (71 meningioma, 133 vestibular schwannoma/VS, 150 arteriovenous malformation/AVM, 76 pituitary adenoma/PA treated with GKRS between December 2013 and May 2023) were analyzed for target coverage (TC), conformity index (CI), homogeneity index (HI), and gradient index (GI)., Result: The values of CIPaddick and CILomax for PA were lower and differed significantly from meningioma, VS, and AVM. The value of HI for PA was higher and differed significantly when compared with meningioma, VS, and AVM. The values of HI for AVM were also significantly higher than VS and meningioma. The mean GI was 3.02, 2.92, 3.03, and 2.88 for meningioma, VS, AVM, and PA, respectively. The value of GI for meningioma and AVM was significantly higher when compared with the values for VS and PA. The mean TC was 0.94 for meningioma, 0.96 for VS, 0.95 for AVM, and 0.90 for PA. The value TC of PA was lower and differed significantly when compared with VS, AVM, and meningioma. Lesions with a volume of ≤1 cc had poor planning metrics as the spillage of radiation may be higher., Conclusion: The GKRS planning parameters depend on the size, shape, nature, and location of intracranial lesions. Therefore, each treatment plan needs to be evaluated thoroughly and a long-term follow-up is needed to establish their relation with clinical outcome., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

This multicenter retrospective cohort study aimed to evaluate the effectiveness of the retrosigmoid surgical approach in decompressing vestibular schwannomas, focusing on tumor decompression, neurological function preservation, and postoperative complications. A cohort of 60 patients, operated between 2016 and 2019, was analyzed for age, sex, symptoms, tumor size, surgery duration, complications, mortality, and facial/auditory functions using established criteria. Hearing loss was observed in 80% of patients, mainly progressive, with tumor size emerging as a critical prognostic factor. Facial weakness affected 10% of patients preoperatively; postoperatively, 35% of patients had affected facial nerve function, with 10% exhibiting poor or no facial nerve function, linked to resection extent rather than tumor size. Tinnitus was more prevalent with larger tumors, whereas headaches were common irrespective of size. Balance disorders improved after surgery, especially in case of larger tumors. Functional recovery varied, with 41.67% of patients returning to their previous activity within 4 months, 25% within 4-12 months, and 33.33% remaining inactive. The mortality rate was low at 3.3 %, with two deaths out of 60 patients after surgery. This analysis highlights surgery risks for vestibular schwannomas (e.g., facial nerve decline, tinnitus, headaches), but also emphasizes benefits like improved balance and low mortality. Many patients regain professional activity, stressing the importance of informed treatment decisions for this condition., Competing Interests: The authors declare no conflict of interest., (© 2024 by the authors.)

Ancient schwannoma (AS) is a subtype of schwannoma characterized by slow progression despite degenerative changes in pathology. Although it is considered a benign tumor, most previous reports have focused on extracranial AS; therefore, the clinical characteristics of intracranial AS is not clear. We included 174 patients who underwent surgery for sporadic intracranial schwannoma, and 13 patients (7.5%) were diagnosed with AS. Cysts were significantly more common in patients with AS than conventional schwannomas (92.3% vs. 44.7%, p < 0.001), as was bleeding (38.5% vs. 6.9%, p = 0.003) and calcification (15.4% vs. 1.3%, p = 0.029). The maximum tumor diameter was also larger in patients with AS (35 mm vs. 29 mm, p = 0.017). The median duration from symptom onset to surgery (7.0 vs. 12.5 months, p = 0.740) did not significantly differ between groups, nor did the probability of postoperative recurrence (p = 0.949). Intracranial AS was strongly associated with cyst formation and exhibited a benign clinical course with a lower rate of recurrence and need for salvage treatment. Extracranial AS is reportedly characterized by a slow progression through a long-term clinical course, whereas intracranial AS did not progress slowly in our study and exhibited different clinical features to those reported for extracranial AS., (© 2024. The Author(s).)

Objectives: The aim was to analyze the long-term hearing results after simultaneous microsurgical extirpation via enlarged cochleostomy and cochlear implantation in intracochlear schwannoma as compared with non-tumor single-side deafness patients., Methods: Microsurgical extirpation via enlarged cochleostomy with simultaneous cochlear implantation was performed in 15 cases of intracochlear schwannoma between 2014 and 2021. Speech recognition tests in German language and impedance performances were collected over 36 months of observation and compared with an internal cohort of 52 age matched non-tumor single-side deafness patients. Retrospective cohort study in a tertiary referral center., Results: The surgery proved feasible and uneventful in all cases. In the case of intracochlear schwannoma, the hearing rehabilitation results were highly satisfactory and comparable to those of the non-tumor single-side deafness cohort. The speech recognition performance improved steadily in the first 12 months; afterward, it remained stable, providing indirect evidence against tumor recurrence during the follow-up. One patient required implant revision surgery related to device failure, but no recurrence was registered in the 36 months of observation., Conclusions: Cochlear implantation is the strategy of choice for hearing rehabilitation in case of intracochlear schwannomas in the long term. In particular, the combination of tumor extirpation via cochleostomy with a cochlear implantation in the same surgical time offers a viable therapy for intracochlear schwannoma, granting a sufficient degree of radicality without compromising the cochlear integrity. This technique allows for revision surgery if required., Level of Evidence: 4 Laryngoscope, 134:1854-1860, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle and internal auditory canal. Illustrating the heterogeneous cellular components of VS could provide insights into its various growth patterns., Methods: Single-cell RNA sequencing was used to profile transcriptomes from 7 VS samples and 2 normal nerves. Multiplex immunofluorescence was employed to verify the data set results. Bulk RNA sequencing was conducted on 5 normal nerves and 44 VS samples to generate a prediction model for VS growth., Results: A total of 83 611 cells were annotated as 14 distinct cell types. We uncovered the heterogeneity in distinct VS tumors. A subset of Schwann cells with the vascular endothelial growth factor biomarker was significantly associated with fast VS growth through mRNA catabolism and peptide biosynthesis. The macrophages in the normal nerves were largely of the M2 phenotype, while no significant differences in the proportions of M1 and M2 macrophages were found between slow-growing and fast-growing VS. The normal spatial distribution of fibroblasts and vascular cells was destroyed in VS. The communications between Schwann cells and vascular cells were strengthened in VS compared with those in the normal nerve. Three cell clusters were significantly associated with fast VS growth and could refine the growth classification in bulk RNA., Conclusions: Our findings offer novel insights into the VS microenvironment at the single-cell level. It may enhance our understanding of the different clinical phenotypes of VS and help predict growth characteristics. Molecular subtypes should be included in the treatment considerations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To derive and validate a prognostic nomogram for the prediction of hearing preservation (HP) after retrosigmoid approach (RSA) in patients with vestibular schwannoma (VS) and further assist in clinical decision-making., Study Design: Retrospective study., Setting: Tertiary referral center., Patients: A total of 111 patients diagnosed with VS with serviceable hearing from January 2013 to March 2023., Interventions: All patients underwent surgery via RSA, and hearing outcomes were reviewed 2 weeks postoperatively., Main Outcome Measures: Preoperative and postoperative hearing were analyzed and stratified according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS)., Results: In multivariate analysis of the primary group, preoperative hearing, tumor size, and tumor origin were significantly related to postoperative HP ( p = 0.029, p = 0.043, and p = 0.018, respectively). Factors derived from the multivariate analysis were all assembled into the nomogram. The receiver operating characteristic (ROC) curves showed good predictive accuracy of the nomogram model in both primary and validation groups with area under the ROC curve (AUC) values of 0.802 and 0.797, respectively., Conclusion: Independent predictors of postoperative HP in patients with VS were selected to create the nomogram. The nomogram was able to stratify patients into different risk groups and assist in clinical decision making., (Copyright © 2024, Otology & Neurotology, Inc.)

Objectives: This study compared the immune-related secretory capacity of human vestibular schwannoma (VS) and tumor-assisted macrophages (TAMs) with their normal counterparts (Schwann cells [SC] and peripheral blood monocyte-derived macrophages [Mo-MFs], respectively), and examined relationships with presurgical hearing and tumor size., Methods: VS tumors (n = 16), auditory nerve (n = 1), blood (n = 9), and great auricular nerves (n = 3) were used. SCs (S100B + ) and TAMs (CD68 + ) were isolated from VS tissue for culture. The secreted levels of 65 immune-related factors were measured and compared using unpaired t-tests with Welch correction (schwannoma vs. SCs) or Mann-Whitney tests (TAMs and Mo-MFs). Associations between factor concentration and word recognition (WR), pure-tone average (PTA), and tumor size were evaluated with Spearman correlation., Results: Secreted factors with significantly higher concentrations in schwannoma versus SC supernatants included IL-2 and BAFF, whereas MMP-1, IL-6, FGF-2, VEGF-A, MIP-3α, and GRO-α concentrations were significantly higher in TAMs versus Mo-MFs (all p < 0.05). Worse WR was significantly associated with higher secretion of fractalkine, eotaxin-3, CD30, and IL-16 by VS cells; IP-10, eotaxin-3, multiple interleukins, GM-CSF, SCF, and CD30 by TAMs; and TNF-α and MIP-1α by Mo-MFs (all p < 0.05). Worse PTA was significantly correlated with higher secretion of IL-16 by VS cells (p < 0.05). Larger tumor size was significantly correlated with higher secretion of eotaxin by VS cells, and of IL-7, IL-21, and LIF by TAMs (all p = 0.017)., Conclusions: Differential secretion of immune-related factors was observed in schwannoma versus normal SCs and in TAMs versus Mo-MFs, some of which were correlated with worse hearing and larger VS tumors., Level of Evidence: N/A Laryngoscope, 134:S1-S14, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: This study aimed to investigate the perilymph metabolism by analyzing the 3D real IR MR findings in acoustic neuroma (AN) after intravenous administration of gadolinium (Gd)., Methods: Eleven patients (6 men and 5 women) diagnosed with AN were included, and 3D real IR MRI was performed 4 hours after intravenous Gd injection. The signal intensity and details of inner ear, tumor, and internal auditory canal (IAC) by MRI were analyzed., Results: Four patients had tumors confined to the IAC, and 5 had tumors that extended to the cerebellopontine angle cistern. The signal intensity of the cochlea, vestibule, and IAC fundus was conspicuously enhanced in 3D real IR images than the control side. One patient had a tumor in the cochlea, in which the signal intensity of the semicircular canal and vestibule was increased. One patient had an intravestibular tumor in which the signal intensity of the semicircular canal was increased and the cochlea had endolymphatic hydrops in the affected ear., Conclusions: The synchronously increased signal intensity in the inner ear and IAC may indicate that IAC may serve as a channel for removal of the perilymph in the inner ear; the blockage by the tumor may have changed the hydrodynamics of the perilymph to cause a longer retention of Gd in the inner ear., Competing Interests: Declaration of Conflicting InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To describe the characteristics, management, and outcomes of pediatric patients with sporadic vestibular schwannoma (sVS)., Methods: This was a case series at a tertiary care center. Patients were identified through a research repository and chart review. Interventions were microsurgery, stereotactic radiosurgery (SRS), and observation. Outcome measures were tumor control, facial nerve function, and hearing., Results: Eight patients over 2006-2022 fulfilled inclusion criteria (unilateral VS without genetic or clinical evidence of neurofibromatosis type 2 (NF2); age ≤ 21) with a mean age of 17 years (14-20). Average greatest tumor length in the internal auditory canal was 9.7 mm (4.0-16.1). Average greatest tumor dimension (4/8 tumors) in the cerebellopontine angle was 19.1 mm (11.3-26.8). Primary treatment was microsurgery in five (62.5%) patients, observation in two (25%), and SRS in one (12.5%). Four (80%) surgical patients had gross total resections, and one (20%) had regrowth post-near total resection and underwent SRS. One observed patient and the primary SRS patient have remained radiographically stable for 3.5 and 7 years, respectively. The other observed patient required surgery for tumor growth after 12 months of observation. Two surgical patients had poor facial nerve outcomes. All post-procedural patients developed anacusis. Mean follow-up was 3 years (0.5-7)., Conclusions: We describe one of the largest reported cohorts of pediatric sVS in the USA. Diligent exclusion of NF2 is critical. Given the high likelihood of eventually requiring intervention and known adverse effects of SRS, microsurgery remains the preferred treatment. However, observation can be considered in select situations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To improve hearing function after resection of large vestibular schwannomas, we describe a strategy of vestibular-nerve-fiber preservation. Anatomical considerations and stepwise dissection are described., Method: Steps include locating the vestibular nerve at the brainstem and identifying a dissection plane between nerve fibers and tumor capsule. Using this plane to mobilize and resect tumor reduced manipulation and maintained vascularity of underlying cochlear and facial nerves., Conclusion: Preservation of hearing function is feasible in large vestibular schwannomas with vestibular-nerve-fiber preservation. Reducing manipulation and ischemic injury of underlying cochlear and facial nerves thereby helped facilitate hearing preservation, even in large tumors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Stereotactic radiosurgery (SRS) is a well-established treatment option for Koos stage I-III vestibular schwannomas (VS), often used as the first line of treatment or after subtotal resection. However, the optimal treatment for Koos-IV VS remains unclear. Therefore, our study aimed to evaluate the effectiveness of SRS as a primary treatment for large VS classified as Koos-IV., Methods: A systematic search was performed on December 28th, 2022, based on PubMed, Web of Science, and Scopus according to the PRISMA statement. The review was updated on September 7th, 2023. The risk of bias was assessed using the NIH Quality Assessment Tool. The R software (ver. 4.3.2) was used for all quantitative analyses and preparation of the forest plots. Publication bias and sensitivity analysis were performed to evaluate the reliability of the obtained results., Results: Among 2941 screened records, ten studies (1398 patients) have been included in quantitative synthesis. The overall tumor control rate was 90.7% (95%CI 86.3-94.4). Kaplan-Meier estimates of tumor control at 2, 6, and 10 years were 96.0% (95% CI 92.9-97.6%), 88.8% (95% CI 86.9-89.8%), and 84.5% (95% CI, 81.2-85.8%), respectively. The overall hearing preservation rate was 56.5% (95%CI 37-75.1). Kaplan-Meier estimates of hearing preservation rate at 2, 6, and 10 years were 77.1% (95% CI 67.9-82.5%), 53.5% (95% CI 44.2-58.5%), and 38.1% (95% CI 23.4-40.7%), respectively. The overall facial nerve preservation rate was 100% (95%CI 99.9-100.0). The overall trigeminal neuropathy rate reached 5.7% (95%CI 2.9-9.2). The overall rate of new-onset hydrocephalus was 5.6% (95%CI 3-9). The overall rates of worsening or new-onset tinnitus and vertigo were 6.8% (95%CI 4.2-10.0) and 9.1% (95%CI 2.1-19.6) respectively. No publication bias was detected according to the used methods., Conclusions: Our systematic review and meta-analysis demonstrated a high overall tumor control rate, excellent facial nerve preservation, and low incidence of new-onset or worsened tinnitus and vertigo. However, several drawbacks associated with SRS should be noted, such as the presence of post-SRS hydrocephalus risk, mediocre long-term hearing preservation, and the lack of immediate tumor decompression. Nevertheless, the use of SRS may be beneficial in appropriately selected cases of Koos-IV VS. Moreover, further prospective studies directly comparing SRS with surgery are necessary to determine the optimal treatment for large VS and verify our results on a higher level of evidence. Registration and protocol: CRD42023389856., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background and Objectives: Intratumoral hemorrhage (ITH) in vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is exceedingly rare. The aim of this study was to define its incidence and describe its management and outcomes in this subset of patients., Methods: A retrospective multi-institutional study was conducted, screening 9565 patients with VS managed with SRS at 10 centers affiliated with the International Radiosurgery Research Foundation., Results: A total of 25 patients developed ITH (cumulative incidence of 0.26%) after SRS management, with a median ITH size of 1.2 cm 3 . Most of the patients had Koos grade II-IV VS, and the median age was 62 years. After ITH development, 21 patients were observed, 2 had urgent surgical intervention, and 2 were initially observed and had late resection because of delayed hemorrhagic expansion and/or clinical deterioration. The histopathology of the resected tumors showed typical, benign VS histology without sclerosis, along with chronic inflammatory cells and multiple fragments of hemorrhage. At the last follow-up, 17 patients improved and 8 remained clinically stable., Conclusion: ITH after SRS for VS is extremely rare but has various clinical manifestations and severity. The management paradigm should be individualized based on patient-specific factors, rapidity of clinical and/or radiographic progression, ITH expansion, and overall patient condition., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: A subset of vestibular schwannomas (VSs), including cystic tumors, have higher postoperative morbidity because of the presence of adhesions between the tumor, facial nerve (FN), and brainstem. We identify tumor microenvironment (TME) biomarkers to better classify these tumors and predict the degree of tumor adherence., Study Design: Retrospective case series., Setting: Tertiary skull base referral center., Methods: Adult patients with cystic and solid VS matched in tumor size who underwent surgical resection were included. Expressions of seven biomarkers of extracellular matrix remodeling and tumor immune response were quantified via immunohistochemistry. The distribution of CD45+ immune cells was evaluated in intratumoral and perivascular compartments. The degree of tumor adherence was categorized as none, adherent to FN, or adherent to both FN and brainstem., Results: Twenty-eight patients were included. Cystic VSs were significantly more adherent than solid VSs ( p = 0.02). Patients with adherent VS had shorter duration of symptoms and were more likely to undergo subtotal resection. In solid tumors, matrix metalloproteinase (MMP)-2 expression ( p = 0.02) and CD163+ macrophage infiltration ( p = 0.007) were correlated with tumor size. Linear discriminant analyses (LDAs) demonstrated MMP-2, MMP-14, CD80, CD163, and perivascular CD45 to be individually predictive of the degree of tumor adherence (all p < 0.05), with perivascular CD45 being the best independent predictor ( p = 0.005). An LDA model including these biomarkers demonstrated 100% accurate discrimination of all three levels of tumor adherence ( p = 0.04)., Conclusions: Adherent VS have a distinct proinflammatory TME characterized by elevated MMP expression, enrichment of tumor-associated macrophages, and perivascular immune cell infiltration., Competing Interests: Conflicts of Interest: None declared., (Copyright © 2023, Otology & Neurotology, Inc.)

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted., (© 2023. The Author(s).)

Objective: Cystic vestibular schwannomas (cVSs) have more variable and less favorable clinical outcomes after microsurgical resection compared with solid VS (sVS). This study compares the preoperative presentation and postoperative outcomes between cVS and sVS., Study Design: Retrospective cohort study., Setting: Two tertiary skull base referral centers., Methods: Consecutive adult patients who underwent VS resection from 2016 to 2021 were included. Univariate and multivariate analyses compared differences in baseline symptoms and postoperative outcomes between cVS and sVS., Results: There were a total of 315 patients (64% female; mean age, 54 yrs) and 46 (15%) were cystic. cVS were significantly larger than sVS (maximum diameter, 28 vs. 18 mm, p < 0.001) and had higher rates of dysphagia and dysphonia preoperatively (p < 0.02). cVSs were more likely to undergo translabyrinthine resection (76 vs. 50%, p = 0.001) and have a higher rate of subtotal resection (STR) compared with sVS (30 vs. 13%, p = 0.003). At latest follow-up, fewer cVS achieved good facial nerve (FN) outcome (House-Brackmann [HB] I/II) (80 vs. 90%, p = 0.048). Subanalysis of cVS and sVS matched in tumor size, and surgical approach did not show differences in the rate of STR or FN outcomes (HB I/II, 82 vs. 78%, p = 0.79)., Conclusion: In this large multi-institutional series, cVSs represent a distinct entity and are characterized by larger tumor size and higher incidence of atypical symptoms. Although cVSs were more likely to undergo STR and portend worse FN outcomes than sVSs, this may be due to their larger tumor size rather than the presence of the cystic component., Competing Interests: Conflicts of interest and source of funding: None declared., (Copyright © 2023, Otology & Neurotology, Inc.)

Objective: To compare cochlear implant (CI) and auditory brainstem implant (ABI) performance in patients with NF2-related schwannomatosis (NF2)., Study Design: Historical cohort., Setting: Tertiary academic center., Patients: A total of 58 devices among 48 patients were studied, including 27 ABIs implanted from 1997 to 2022 and 31 CIs implanted from 2003 to 2022. Three patients had bilateral ABIs, three had bilateral CIs, three had an ABI on one side and a CI on the other, one had a CI that was later replaced with an ipsilateral ABI, and one had an ABI and CI concurrently on the same side., Interventions: CI or ABI ipsilateral to vestibular schwannoma., Main Outcome Measures: Open-set speech perception, consonant-nucleus-consonant word scores, and AzBio sentence in quiet scores., Results: Among all patients, 27 (47%) achieved open-set speech perception, with 35 (61%) daily users at a median of 24 months (interquartile range [IQR], 12-87 mo) after implantation. Comparing outcomes, CIs significantly outperformed ABIs; 24 (77%) CIs achieved open-set speech perception compared with 3 (12%) ABIs, with median consonant-nucleus-consonant and AzBio scores of 31% (IQR, 0-52%) and 57% (IQR, 5-83%), respectively, for CIs, compared with 0% (IQR, 0-0%) and 0% (IQR, 0-0%), respectively, for ABIs. Patients with ABIs were younger at diagnosis and at implantation, had larger tumors, and were more likely to have postoperative facial paresis., Conclusion: Many patients with NF2-associated vestibular schwannoma achieved auditory benefit with either a CI or an ABI; however, outcomes were significantly better in those patients who were able to receive a CI. When disease and anatomy permit, hearing rehabilitation with a CI should be considered over an ABI in these patients. Tumor management strategies that increase the ability to successfully use CIs should be strongly considered given the high risk of losing bilateral functional acoustic hearing in this population., (Copyright © 2023, Otology & Neurotology, Inc.)

Introduction: The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding cochlear nerve damage by transient volume expansion of VSs after radiosurgery and radiation-induced cochlear damage. This study aimed to investigate whether there is a specific patient population that can achieve definite hearing preservation after SRS for VSs., Methods: A total of 37 consecutive patients with sporadic unilateral intracanalicular VSs and serviceable hearing (Gardner-Roberson [G-R] class I or II) were treated with SRS from 2009 to 2023. This is a retrospective study. Survival analysis with Cox regression for hearing deterioration was performed., Results: The median age was 55 years old. The median tumor volume was 0.089 cm 3 , and the median marginal dose was 12.0 Gy. Nonserviceable hearing deterioration occurred in 9 patients (24.3%), with a median onset of 11.9 months after SRS. The actuarial rates of serviceable hearing preservation were 86%, 82%, and 70% at 1, 2, and 3 years after SRS, respectively. In a multivariate analysis, only baseline pure tone average > 30 dB increased the risk of nonserviceable hearing deterioration with significant hazard ratio. There were 13 patients with petit VSs whose tumor volume was smaller than 0.05 cm 3 , and 11 of them were treated by a 4-mm single shot with a marginal dose of 12 Gy. None of the 13 patients had nonserviceable hearing deterioration., Conclusions: Petit VSs that can be treated with 4-mm single or double shots with a marginal dose of 12 Gy may achieve hearing preservation after SRS., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Importance: Over the past decades, the number of patients, especially in the older adult patient group, diagnosed with vestibular schwannoma (VS) has increased. Assuming that older adult patients have more comorbidities, a longer recovery period after surgery, a higher rate of surgical complications, and a higher mortality rate after VS surgery, a treatment strategy for this group of patients is warranted, based on clinical evidence on postsurgical survival., Objective: To evaluate the survival after diagnosis of a VS in patients 70 years and older, treated with either observation or surgery, and to compare these findings with the life span of an age-matched background population in Denmark., Design, Setting, and Participants: This was a retrospective cohort study of 624 patients 70 years and older diagnosed with VS in Denmark from 1976 to 2016. Since 1976, all patients with a VS have been registered in a national database, which contains 3637 patients. Of the included patients in this study, 477 were treated conservatively with the "wait-and-scan" strategy, and 147 were treated surgically with removal of the tumor. The survival of the patients was compared with a matched background population in Denmark. Data analysis was performed from January 1976 to January 2017., Exposures: Surgery, radiotherapy, or none., Main Outcomes and Measures: The main outcome was survival among the patients and compared with the matched background population., Results: A total of 624 patients were included (317 female patients [50.8%] and 307 male patients [49.2%]). The mean (SD) survival in the observed patients was 9.2 (4.7) years after diagnosis, whereas for the background population, the expected survival was 11 years from the mean age at diagnosis. For the surgically treated patients, the mean (SD) survival was 11.8 (6.6) years, and expected survival was 11 years for the matched background population. The mean (SD) survival was 10.7 (5.5) years in female patients and 8.9 (5.0) years in male patients. There was no significant difference in survival between treatment modalities, irrespective of tumor size., Conclusions and Relevance: In this cohort study, survival after diagnosis of a VS in patients 70 years and older was similar in the surgical group compared with the age-matched background population. In the wait-and-scan group, the survival after diagnosis was marginally shorter, which may be associated with increased comorbidity.