Vestibular Schwannoma Patients Research Articles

QOL-05. COMPARING DISEASE-SPECIFIC QUALITY-OF-LIFE OUTCOMES OF MICROSURGERY, RADIOTHERAPY, AND OBSERVATION IN VESTIBULAR SCHWANNOMA PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND Vestibular schwannoma (VS), also known as acoustic neuromas, are common tumors arising from the vestibulocochlear nerve and are located in the cerebellopontine angle. The benign tumor has a substantial impact on the patient-perceived quality of life (QoL) outcomes, which contribute to the decision regarding the ideal management plan. In this systematic review and meta-analysis, we aimed to compare the impact of microsurgery, radiotherapy, and observation on the QoL outcomes of VS patients. METHODS This study was conducted in accordance with the PRISMA guidelines and a total of four research databases were searched for eligible studies from inception to May 2024. The primary outcome of the study was the Penn Acoustic Neuroma Scale (PANQOL) total score and the secondary outcomes included the PANQOL subdomain scores. Data was pooled using the random-effects model and analyzed as OR (odds ratio) with 95% CI (confidence interval). RESULTS Compared to observation, radiotherapy was associated with superior QoL outcomes only in the face domain [MD (mean difference) = -4.59 [-7.29,-1.88]; I2= 85%; p = 0.0001], with observation being associated with superior outcomes across all others [PANQOL - total: MD = 4.94 [2.51,7.38]; I2= 85%; p = 0.0001]. Microsurgery, compared to radiotherapy, was associated with better outcomes only in the general domain [MD = -4.38 [-6.60,-2.16]; I2= 0%; p = 0.0001], with RT being associated with superior outcomes across all other domains [PANQOL - total: MD = 3.61 [1.29,5.93]; I2= 63%; p = 0.002]. Compared to microsurgery, observation was associated with superior QoL outcomes across all domains [PANQOL - total: MD = 9.22 [7.30,11.13]; I2= 64%; p = 0.0001]. CONCLUSION The findings indicate that, broadly, observation is associated with better QoL outcomes relative to both radiotherapy and microsurgery; with radiotherapy superseding microsurgery. However, the association with QoL improvement was not uniform across all domains.

Exploring the Role of Inflammatory Genes and Immune Infiltration in Vestibular Schwannomas Pathogenesis.

Vestibular schwannomas (VSs) exhibit a range of tumor behaviors, such as growth patterns and auditory dysfunction. Recent research has offered insights into the inflammatory microenvironment in modulating tumor dynamics. This study investigates the role of inflammatory genes and immune infiltration in VS pathogenesis. We retrieved mRNA microarray data of VSs and normal nerves from the GEO database (GSE141801, GSE108524, and GSE56597), focusing on bioinformatic analysis of inflammatory response genes. Based on the evidence provided by bioinformatics analysis, we assessed the expression levels of Iba-1, IL-10, IL-10RA, and IL-18 in 31 VS patients via immunohistochemistry and delved into their association with tumor size and auditory dysfunction. We identified 1117 differentially expressed genes (DEGs) in VSs compared to normal nerves, showing an upregulation in inflammatory pathways. Intersection with inflammatory response genes (IRG) yielded 41 significant IRG-DEGs. Network analysis identified a core module of 10 IRG-DEGs and 11hub genes, most of which were inflammatory cytokines. Immune infiltration analysis showed macrophage activation and M2 polarization. These findings were validated in an independent dataset (GSE39645). To further explore the association between inflammation and tumor behaviors, immunohistochemistry analysis was conducted on VS samples and the results exhibited notable associations between the macrophage marker (Iba1) and inflammatory cytokines (IL-10, IL-10RA, and IL-18) with both tumor size and auditory dysfunction. In particular, the multiple regression analysis of inflammatory cytokines demonstrated that IL-10 and IL-10RA were statistically significant predictors of tumor size, while IL-18 was associated with hearing loss. Our study underscores the role of inflammation in VS pathogenesis, showing that macrophage activation with M2 polarization and the expression of inflammatory cytokines, especially IL-10/IL-10RA and IL-18, are linked to tumor size and auditory function. This study highlights the inflammatory landscape's impact on VS behaviors, providing a basis for targeted therapeutic strategies.

Effectiveness of CI as an alternative to ABI for hearing loss in patients with vestibular schwannomas: A multicenter study in Japan

ObjectiveNF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS), often causing severe damage to the bilateral auditory function. Auditory brainstem implantation (ABI) provides hearing-impaired patients with an opportunity to reacquire auditory sensation through electrical stimulation of auditory neurons in the cochlear nucleus. However, ABI is not covered by public health insurance in Japan, leading to a large difference in financial burden compared to cochlear implantation (CI). The aim of the present study was to demonstrate the effectiveness of CI as an alternative to ABI for hearing reacquisition in patients with profound hearing loss caused by VS. MethodsTo investigate the current situation of ABI and CI for hearing reconstruction in VS patients, we conducted a questionnaire survey of 102 facilities in Japan. Based on the responses to the questionnaire, a multicenter research group consisting of otolaryngologists and neurosurgeons was established. We collected detailed data on patients with VS who underwent ABI (n = 7, all NF2) and CI (n = 14 [nine NF2, and five non-NF2]). ResultsSome sense of hearing was obtained in all patients but one with CI indicating the efficacy of CI and ABI for profound hearing loss caused by VS. The mean hearing levels were 45.4 dB HL in the ABI patients and 32.7 dB HL in the CI patients, indicating that CI was effective as an alternative to ABI. ConclusionThe results of the present study suggest the effectiveness of CI as an alternative to ABI for hearing reacquisition in patients with profound hearing loss caused by VS. Level of evidence4.

Cancer-Associated Fibroblast Subtypes Reveal Distinct Gene Signatures in the Tumor Immune Microenvironment of Vestibular Schwannoma.

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.

Predictors of Prolonged Hospital Stay After Microsurgery for Vestibular Schwannoma: Analysis of a Decade of Data.

Microsurgical resection is one of the treatments for vestibular schwannomas (VS). While several factors have been linked to increased length of stay (LOS) for VS patients undergoing microsurgery, a better understanding of these factors is important to provide prognostic information for patients. Determine predictors of increased LOS for VS patients undergoing microsurgical resection. Retrospective analysis using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2010 to 2020. Database review. All patients who underwent microsurgery (CPT codes 61520, 61526/61596) for the management of vestibular schwannoma (ICD9 and ICD10 codes 225.1, D33.3) were included. Analyzing perioperative factors that can predict prolonged hospital stay. A total of 2096 cases were identified and 1,188 (57%) of these patients were female. The mean age was 51.0 ± 14.0 years. Factors contributing to prolonged LOS included African American race (OR = 2.11, 95% CI: 1.32-3.36, p = 0.002), insulin-dependent diabetes mellitus (OR = 2.12, 95% CI: 1.09-4.4.11, p = 0.026), hypertension (OR = 1.26, 95% CI: 1-1.58, p = 0.046), functional dependency (OR = 5.22, 95% CI: 2.31-11.79, p = 0.001), prior steroid use (OR = 1.96, 95% CI: 1.18-3.15, p = 0.009), ASA class III (OR = 2.06, 95% CI: 1.18-3.6, p < 0.011), ASA class IV (OR = 6.34, 95% CI: 2.62-15.33, p < 0.001), and prolonged operative time (OR = 2.14, 95% CI: 1.76-2.61). Microsurgery by a translabyrinthine (TL) approach compared to a retrosigmoid (RSG) approach had lower odds of prolonged LOS (OR = 0.67, 95% CI: 0.54-0.82, p < 0.001). In a separate analysis regarding patients receiving reoperation, operative time was the only predictor of prolonged LOS (OR = 2.77, 95% CI: 1.39-5.53, p = 0.004.). Our analysis offers an analysis of the factors associated with a prolonged LOS for the surgical management of VS. By identifying healthcare disparities, targeting modifiable factors, and applying risk stratification based on demographics and comorbidities, we can work toward reducing disparities in LOS and enhancing patient outcomes.

Correlation of Immunomodulatory Cytokines with Tumor Volume and Cerebrospinal Fluid in Vestibular Schwannoma Patients.

Sporadic vestibular schwannomas (VSs) often exhibit slow or negligible growth. Nevertheless, some VSs increase significantly in volume within a few months or grow continuously. Recent evidence indicates a role of inflammation in promoting VS growth. Therefore, our study aimed to identify cytokines, which are associated with larger VSs. The expression of different cytokines in VS tumor samples and VS primary cultures was investigated. Additionally, the concentration of cytokines in cell culture supernatants of VS primary cultures and cerebrospinal fluid (CSF) of VS patients and healthy controls were determined. Correlation analysis of cytokine levels with tumor volume, growth rate, Koos grade, age, and hearing was examined with Spearman's-rank test. The mRNA expression of CC-chemokine ligand (CCL) 18, growth differentiation factor (GDF) 15, and interferon regulatory factor 4 correlated positively with tumor volume. Moreover, the amount of GDF15 in the cell culture supernatant of primary cells correlated positively with tumor volume. The concentrations of the cytokines CCL2, CCL5, and CCL18 and transforming growth factor beta (TGFB) 1 in the CSF of the patients were significantly different from those in the CSF controls. Inhibition of immune cell infiltration could be a putative approach to prevent and control VS growth.

Is galvanic VEMP a prediction of the nerve origin and damage in patients of vestibular schwannoma

Background Recent studies proved that certain proportions of vestibular schwannoma (VS) originated other than vestibular nerve of the eighth cranial nerve. Aims/objectives Unlike air-conducted sounds (ACS) and bone-conducted vibration (BCV), galvanic vestibular stimulation (GVS) evokes vestibular evoked myogenic potentials (VEMPs) from the vestibular nerve. Materials and methods Case-control study was conducted in unilateral VS patients pre-operatively. Healthy ears were controls. Patients examined ACS, BCV and GVS ocular VEMP (oVEMP) and cervical VEMP (cVEMP), caloric test, video head impulse test (vHIT), suppression head impulse paradigm (SHIMP) and pure tone audiometry (PTA). Results Seven (26.9%) tumors affected left ear and 19 (73.1%) on the right(p < .05). Response rates in VS group were statistically lower than control except for ACS-cVEMP (p < .05). Response rates of VEMPs in VS patients decreased with the tumor size grows. But not all BCV and GVS VEMPs disappeared in the largest tumor group. Abnormal rates of caloric test, vHIT gains and SHIMP were found. Conclusions and significance Response rates of GVS VEMPs decreased with the residual functional nerve fibers. GVS VEMPs help to differentiating labyrinthine and retro-labyrinthine lesions. GVS combined with BCV VEMPs probably reflex the tumor origin from the eighth cranial nerve and/or the remaining vestibular function.

Assessing the stability and discriminative ability of radiomics features in the tumor microenvironment: Leveraging peri-tumoral regions in vestibular schwannoma

PurposeThe tumor microenvironment (TME) plays a crucial role in tumor progression and treatment response. Radiomics offers a non-invasive approach to studying the TME by extracting quantitative features from medical images. In this study, we present a novel approach to assess the stability and discriminative ability of radiomics features in the TME of vestibular schwannoma (VS). MethodsMagnetic Resonance Imaging (MRI) data from 242 VS patients were analyzed, including contrast-enhanced T1-weighted (ceT1) and high-resolution T2-weighted (hrT2) sequences. Radiomics features were extracted from concentric peri-tumoral regions of varying sizes. The intraclass correlation coefficient (ICC) was used to assess feature stability and discriminative ability, establishing quantile thresholds for ICCmin and ICCmax. ResultsThe identified thresholds for ICCmin and ICCmax were 0.45 and 0.72, respectively. Features were classified into four categories: stable and discriminative (S-D), stable and non-discriminative (S-ND), unstable and discriminative (US-D), and unstable and non-discriminative (US-ND). Different feature groups exhibited varying proportions of S-D features across ceT1 and hrT2 sequences. The similarity of S-D features between ceT1 and hrT2 sequences was evaluated using Jaccard’s index, with a value of 0.78 for all feature groups which is ranging from 0.68 (intensity features) to 1.00 (Neighbouring Gray Tone Difference Matrix (NGTDM) features). ConclusionsThis study provides a framework for identifying stable and discriminative radiomics features in the TME, which could serve as potential biomarkers or predictors of patient outcomes, ultimately improving the management of VS patients.

Labyrinthectomy Improves Dizziness in Patients with Vestibular Schwannoma

Abstract Objective Dizziness is one of the most prevalent and debilitating symptoms associated with vestibular schwannoma (VS), and there are little data on contributing or alleviating factors in the perioperative setting. In this study, we aimed to evaluate whether vestibular nerve sectioning or labyrinthectomy concomitant with surgical resection would improve dizziness in the postoperative period. Methods This is a retrospective study of a consecutive series of VS patients who underwent resection at a large tertiary care center between 2009 and 2023. Dizziness at 6 months was the primary endpoint, whereas facial nerve and hearing outcomes were secondary endpoints. Fisher's exact test was used to identify significant differences between categorical variables, and multivariate logistic regression analysis was performed to identify predictors of dizziness as well as facial nerve and hearing outcomes. Results A total of 333 patients underwent resection of VS at our institution. There was no significant difference in binary reported dizziness based on surgical approach (p = 0.14). However, patients reported significantly less dizziness at discharge (p &lt; 0.01) as well as 6-month (p = 0.02) and 1-year (p &lt; 0.01) follow-up in the translabyrinthine group. On the other hand, patients who underwent labyrinth-sparing approaches reported a significant increase in dizziness that remained up to 1 year from the time of surgery. Conclusions Our data suggest that labyrinthectomy may improve dizziness symptoms in patients with VS. Selective VN sectioning does not appear to affect dizziness or hearing outcomes. Finally, surgical approach does not affect facial nerve outcomes.

Long-Term Hearing Outcome For Vestibular Schwannomas After Microsurgery And Radiotherapy: A Systematic Review and Meta-Analysis.

Hearing loss is a common symptom associated with vestibular schwannoma (VS), either because of the tumor's effects on the cochlear nerve or due to active treatments such as surgery or stereotactic radiosurgery (SRS). Treatment decisions for VS are based on factors including tumor size, hearing status, patient symptoms, and institutional preference. The study aimed to investigate long-term auditory outcomes in VS patients undergoing active treatments with a hearing preservation intent. A systematic literature review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching Scopus, Pubmed, and Web of Science databases from inception to January 2024. Studies meeting inclusion criteria, including a minimum 5-year follow-up and assessment of pre- and posttreatment hearing outcomes, were included. Pooled prevalence estimates for serviceable hearing after SRS and microsurgery were calculated using MetaXL software. Risk of bias assessment was performed with the Risk of Bias in Non-randomized Studies of Interventions tool. Nine studies met the inclusion criteria, with 356 patients included for analysis. The pooled prevalence of maintaining serviceable hearing after SRS at 10 years was 18.1% (95% confidence interval [CI]: 1.7%-43.3%), with wide prediction intervals indicating variability in outcomes. Microsurgery demonstrated a higher prevalence of maintaining long-term serviceable hearing, with a pooled estimate of 74.5% (95% CI: 63.5%-84.1%). This systematic review underscores the importance of long-term follow-up in evaluating auditory outcomes in VS treatment. Despite the biases inherent to pretreatment patients selection, hearing preservation microsurgery for sporadic VS removal demonstrated favorable and stable long-term serviceable hearing.

Intraoperative Hearing Monitoring Using ABR and TT-ECochG and Hearing Preservation during Vestibular Schwannoma Resection.

Background: Quick and appropriate diagnostics and the use of intraoperative monitoring (IM) of hearing during vestibular schwannoma (VS) resection increase the likelihood of hearing preservation. During surgery, various methods of IM can be used, i.e., auditory brainstem responses (ABRs), transtympanic electrocochleography (TT-ECochG), and direct cochlear nerve action potentials. The aim of the study was to evaluate the prognostic values of IM of hearing using ABR and TT-ECochG in predicting postoperative hearing preservation and to evaluate relationships between them during various stages of surgery. Methods: This retrospective study presents the pre- and postoperative audiological test results and IM of hearing records (TT-ECochG and ABR) in 75 (43 women, 32 men, aged 18-69) patients with diagnosed VS. Results: The preoperative pure tone average hearing threshold was 25.02 dB HL, while after VS resection, it worsened on average by 30.03 dB HL. According to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Hearing Classification, before and after (pre/post) surgery, there were 47/24 patients in hearing class A, 9/8 in B, 2/1 in C, and 17/42 in D. In speech audiometry, the average preoperative speech discrimination score at an intensity of 60 dB SPL was 70.93%, and after VS resection, it worsened to 38.93%. The analysis of electrophysiological tests showed that before the tumor removal the I-V ABR interlatencies was 5.06 ms, and after VS resection, it was 6.43 ms. Conclusions: The study revealed correlations between worse postoperative hearing and changes in intraoperatively measured ABR and TT-ECochG. IM of hearing is very useful in predicting postoperative hearing in VS patients and increases the chance of postoperative hearing preservation in these patients.

Factors Affecting Speech Discrimination After Vestibular Schwannoma Resection.

Investigate the relationship between word recognition score (WRS) and pure tone average (PTA) after hearing preservation surgery for vestibular schwannomas (VS) as well as evaluate the consistency of hearing classification systems. A retrospective chart review was performed. This study included patients from a single academic tertiary referral hospital. Patients with VS and serviceable hearing who underwent hearing preservation surgery 2014-2023. Patients excluded for neurofibromatosis 2 and lacking pre/postop audiograms. All patients underwent resection of vestibular schwannoma. Pre/postop WRS, PTA, and AAO-HNS, Gardner-Robertson (GR), and WRS Class (WRSC) hearing classifications. Seventy-five patients were included. Average preop and postop PTA and WRS were 26 ± 12 dB, 79 ± 39 dB, 92 ± 12%, and 33 ± 43%, respectively. Postop PTAs were distributed along the complete testable decibel range, while the postop WRS displayed a bimodal distribution, with WRS >50% or <20%. Worsening intraop ABR changes were significantly associated with poorer hearing outcomes ( p = 0.005). With increasing Koos grades, intraop ABRs were significantly more likely to exhibit changes ( p = 0.005). AAO-HNS and GR classified patients nearly identically, while the WRSC resulted in more class I and fewer class II. The cutoff of serviceable hearing was comparable across all classification systems. Effects on the brainstem component of Koos 3-4 tumors may particularly disturb speech processing. This effect seems amplified by surgical dissection. AAO-HNS, GR, and WRSC hearing classifications are comparable in describing serviceable hearing in vestibular schwannoma patients.

Defining tumor growth in vestibular schwannomas: a volumetric inter-observer variability study in contrast-enhanced T1-weighted MRI

PurposeFor 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.MethodsThis 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).ResultsThe 100 patients had a median average tumor volume of 903 mm3 (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).ConclusionAgreement 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 mm3, 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.

Losartan May Not Prevent Vestibular Schwannoma Growth or Related Hearing Loss During Observation.

To evaluate the impact of losartan on vestibular schwannoma (VS) growth and related hearing loss during observation. Retrospective cohort study. Tertiary referral center. Sporadic VS patients undergoing initial observation with at least two magnetic resonance imaging and audiologic examinations. Losartan. Endpoints included VS growth, quantitative audiologic changes, survival free of tumor growth, and survival free of nonserviceable hearing. Patient characteristics and endpoints were compared by losartan use. Seventy-nine patients were included, of which 33% were taking losartan. Tumor growth was observed in 50% of patients in the losartan group and 36% in the non-losartan group (p = 0.329). Survival analysis failed to show a significant difference in the hazard rate of VS growth between groups (hazard ratio, 1.38; 95% confidence interval, 0.70-2.70; p = 0.346). Throughout observation, mean decreases in normalized pure-tone average were 5.5 and 9.3 dB in the losartan and non-losartan groups, respectively (p = 0.908). Mean decreases in normalized word recognition score were 11.0 and 16.6% in the losartan and non-losartan groups, respectively (p = 0.757). Nonserviceable hearing developed in 19% of patients in the losartan group and 28% in the non-losartan group (p = 0.734). Survival analysis did not demonstrate a significant difference in the hazard rate of developing nonserviceable hearing between groups (hazard ratio, 1.71; 95% confidence interval, 0.56-5.21; p = 0.337). Losartan use may not reduce the risk of VS growth or hearing loss during observation. A randomized trial would be ideal to further identify the true effect on growth and hearing.

Vestibular Schwannomas: implementation of PANQOL and Mayo VSQOL Index scales in Ukraine and justification of treatment strategy with preservation of quality of life (problem analysis, own experience, discussion points)

Objective: To evaluate the treatment outcomes of sporadic vestibular schwannomas (VS) to substantiate the choice of optimal treatment strategy considering quality of life indicators using the Penn Acoustic Neuroma Quality of Life Scale (PANQOL) and the Mayo Clinic Vestibular Schwannoma Quality of Life Index (Mayo VSQOL Index) scales in Ukraine. Materials and Methods: 1100 patients with VS were treated at the Subtentorial Neurooncology Department from 2001 to October 2023 and 373 were primarily considered for dynamic observation (“wait-and-scan”) at the Department of Ear Microsurgery and Otoneurosurgery of the Kolomiichenko Otolaryngology Institute. Data on 359 patients (some of whom underwent surgery in the mentioned departments) who received radiotherapy (RT) from 2010 to 2023 in the Radioneurosurgery Department are also provided. The PANQOL and Mayo VSQOL Index scales were implemented to assess the quality of life of patients with VS. Scientific publications from the PubMed database related to the study of the quality of life in patients with VS were analyzed. Results: The analysis was based on patient data from the database for the period 2017 - October 2023, 391 patients with VS were treated, including 359 who underwent surgical treatment (schwannomas resection), 4 – tarsorrhaphy after VS resection, and 28 who received combined treatment (surgery + radiotherapy). A separate group consisted of 359 patients who underwent radiotherapy (RT). Of 177 patients who underwent radiosurgical treatment, 65 (36.7%) had Stage III VS according to the classification of W.T. Koos, and 112 (63.3%) had stage IV VS. Primarily diagnosed tumors were treated in 110 (62.1%) and 67(37.9%) patients with residual postoperative. Follow-up data were obtained for 159 patients. At the Kolomiichenko Otolaryngology Institute, 373 patients were under observation with the primary "wait-and-scan" strategy, of whom 110 (29.5%) had their VS removed due to symptom progression or progressive course, and 24 (6.4%) underwent RT. Of the 27 patients in the Subtentorial Neurooncology Department study group, 7 (25.9%) underwent surgery, and 5 (18.5%) underwent RT. Conclusions: Global practice in assisting patients with VS indicates a shift towards dynamic follow-up and an increase in the frequency of using radiation treatment methods. Over the past years, strategy have been proposed that do not recommend the "wait-and-scan" mode due to the risk of life-threatening complications associated with tumor growth. However, there is very little data on long-term outcomes (more than 5 years) and quality of life. VS primarily detected by magnetic resonance imaging in Ukraine significantly larger (Koos III-IV) than those reported in the literature. The implementation of specialized scales for assessing the quality of life of VS patients in Ukraine will help improve outcomes by applying personalized criteria for treatment routes, increasing the level of awareness and responsibility of both patients and doctors.

Reduced Cochlear MRI Signal and Hearing Outcomes in Conservatively Managed Vestibular Schwannoma Patients.

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. Retrospective review of 657 cases from 1992 to 2020. Tertiary academic referral center. 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. Conservatively managed patients with CISS imaging studies and audiology testing. 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. 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. Abnormal cochlear signal on MRI CISS sequences is associated with poorer hearing outcomes in conservatively managed VS patients.

Tumor biomechanical stiffness by magnetic resonance elastography predicts surgical outcomes and identifies biomarkers in vestibular schwannoma and meningioma

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.

Relationship between vestibular schwannoma and endolymphatic hydrops

BackgroundBoth vestibular schwannoma (VS) and Meniere's disease (MD) patients underwent hydrops MRI to clarify the relationship between VS and endolymphatic hydrops (EH). MethodsEighty 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. ResultsThe 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. ConclusionA 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.

Hearing loss and its association with the proteome of perilymph, cerebrospinal fluid, and tumor tissue in patients with vestibular schwannoma

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.

Age, preoperative tumor volume and widening of the internal acoustic meatus are independent factors associated with poor preoperative hearing in vestibular schwannoma patients – results of a single-center retrospective analysis

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.