Vestibular Schwannoma Research Articles

NF2 is Essential for Human Endoderm Development.

Vertebrate embryogenesis requires the precisely timed specification of 3 germ cell layers- ectoderm, mesoderm, and endoderm- which give rise to tissues and organs in the developing organism. The tumor suppressor gene NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (Nf2) is expressed in all 3 germ layers during mouse development and its homozygous deletion causes embryonic lethality. People with heterozygous NF2 mutations typically develop Schwann cell tumors, especially vestibular schwannoma, but the specific role of NF2 in human embryonic development is unclear. Here, human induced pluripotent stem cells (hiPSCs) are used to demonstrate that NF2 is essential for endoderm specification and formation in humans. Although endoderm differentiation is not impaired in hiPSCs with heterozygous NF2 mutation, NF2 knockout (NF2-/-) abolished the capacity to form endoderm in vitro, confirmed by loss of expression of endoderm-related genes and proteins, or teratomas in vivo. This defect is mediated by the nuclear translocation of yes-associated protein 1 (YAP1), a transcription co-activator regulating lineage fate via the Hippo pathway and subsequent YAP1-mediated shutdown of Activin/Nodal signaling. Endoderm formation can be rescued via YAP1 knockdown or forced re-expression of NF2 in NF2-/- cells. Taken together, the essential role of NF2 during endoderm specification in human embryogenesis as a regulator of YAP1 is reported.

Immune profiling of human vestibular schwannoma secretions identifies TNF-α and TWEAK as cytokines with synergistic potential to impair hearing

BackgroundVestibular schwannoma (VS) is an intracranial tumor arising from the Schwann cells of the vestibular nerve and is an important cause of sensorineural hearing loss (SNHL) in humans. The mechanisms underlying this SNHL are incompletely understood and currently, there are no drugs FDA approved specifically for VS. This knowledge gap significantly limits the development of effective treatments aimed at preventing, stabilizing, or reversing VS-induced SNHL.MethodsTo identify effector molecules involved in VS-induced SNHL, we analyzed 47 immune-related factors secreted by tumor tissue in over 50 patients with sporadic VS and studied their correlation with preoperative hearing ability and tumor size. The most promising effector molecules were validated in vivo in an anatomically accurate mouse model of VS, and in vitro with mouse fibroblasts (L929) and auditory cell lines representing pro-sensory precursors of hair cells (UB-OC1) and auditory neuroblasts (US-VOT-N33).ResultsWe demonstrated that VS-induced SNHL was linked to increased secretion of TNF-α, IL-2R, CD163, eotaxin, and HGF, while larger tumor size was associated with higher levels of TNF-α, TNF-R2, IL-1α, IFN-α, MIP-1β, and IL-21 secretion. We identified heterogeneity among VS tumors in their capacity to secrete TNF-α. Tumors with high levels of TNF-α secretion released cytokines and chemokines that significantly correlated with poor hearing (TWEAK and eotaxin) or better hearing (LIF, GRO-α, MIP-1α, MIP-3α, and IL-1α). Among these, TWEAK was notably abundant, with levels exceeding those in normal nerve tissue, elevated in patients with non-serviceable hearing and strongly linked to poor hearing in patients with TNF-α high-secreting tumors. In vivo, we demonstrated that VS-secreted factors reach the inner ear, with elevated TNF-α and TWEAK in the perilymph and blood of tumor-bearing mice with impaired hearing. In vitro, TWEAK amplified TNF-α -mediated cytotoxicity in TNF-α sensitive cells (L929) and auditory cell lines (UB-OC1 and US-VOT-N33) at tumor-secreted concentrations.ConclusionThis study provides compelling evidence that VS-secreted TNF-α and TWEAK act synergistically to drive tumor-induced SNHL. Targeting the TNF-α/TWEAK axis presents a promising new avenue for preventing VS-induced SNHL.

A simple plan strategy to optimize the biological effective dose delivered in robotic radiosurgery of vestibular schwannomas

Using the concept of biologically effective dose (BED), the effect of sublethal DNA damage repair (SLR) on the bio-efficacy of prolonged radiotherapy treatments can be quantified (BEDSLR). Such treatments, lasting more than 20 min, are typically encountered in stereotactic radiosurgery (SRS) applications using the CyberKnife (CK) and Gamma knife systems. Evaluating the plan data from 45 Vestibular Schwannoma (VS) cases treated with single fraction CK-SRS, this work demonstrates a statistically significant correlation between the marginal BEDSLRdelivered to the target (m-BEDSLR) and the ratio of the mean collimator size weighted by the fraction of total beams delivered with each collimator (wmCs), to the tumor volume (Tv). The correlation betweenm-BEDSLRandwmCsTvdatasets was mathematically expressed by the power functionm-BEDSLR=85.21 (±1.7%)⋅(wmCsTv)(0.05±7%) enabling continuousm-BEDSLRpredictions. Using this formula, a specific range ofm-BEDSLRlevels cana prioribe targeted during treatment planning through proper selection of collimator size(s) for a given tumor volume. Inversely, for a selected set of collimators, the optimization range ofm-BEDSLRcan be determined assuming that all beams are delivered with the smallest and largest collimator size. For single collimator cases or when the relative usage of each collimator size is known or estimated, a specificm-BEDSLRlevel can be predicted within 3% uncertainty. The proposed equation is valid for the fixed CK collimators and a physical dose prescription (Dpr) of 13 Gy. For alternateDprin the range of 11-14 Gy, a linear relationship was found between relative changes ofm-BEDSLR(Dpr) andDprwith respect tom-BEDSLR(13 Gy) and 13 Gy, respectively. The proposed methodology is simple and easy to implement in the clinical setting allowing for optimization of the treatment's bio-effectiveness, in terms of the delivered BED, during treatment planning.

Efficacy and Toxicity of Bevacizumab in Children with NF2-Related Schwannomatosis: A Systematic Review

Background/Objectives: NF2-related schwannomatosis (NF2) is a tumor predisposition syndrome that typically presents with bilateral vestibular schwannomas, together with other intracranial and spinal schwannomas, meningiomas, and/or ependymomas. Bevacizumab, a VEGF inhibitor, has the potential to decrease schwannoma volume and improve hearing in adults, but the literature on the effects in children is sparse. This narrative review aims to evaluate the use of bevacizumab in pediatric NF2 patients, focusing on hearing, tumor progression, and toxicity. Methods: A literature review was conducted following PRISMA guidelines. Articles were searched in PubMed, Embase, Web of Science, Cochrane Library, Emcare, and Academic Search Premier on 18 July 2024. Inclusion criteria were patients ≤ 18 years, diagnosed with NF2 and treated with bevacizumab. Two authors independently assessed the quality of the evidence and extracted relevant data from the included articles. Results: Seventeen articles including 62 pediatric NF2 patients met the inclusion criteria. Studies varied widely in treatment regimens and outcome parameters. Tumor regression was reported in 6/56 patients (11%) and 38/56 (68%) remained stable. Hearing improved in 15/45 patients (33%) and did not further deteriorate in 27/45 (60%). An improvement in other symptoms was seen in 6/29 patients (28%). Toxicity was reported in five studies, documenting 13 adverse events in 28 patients ranging from grade 1 to grade 3. Treatment was discontinued in both patients who experienced grade 3 toxicity. Conclusions: Bevacizumab seems to be a viable treatment option for pediatric NF2 patients. Tumor regression or stabilization is achieved in the majority of patients (77%). Moreover, a considerable number of pediatric patients experience hearing stabilization or improvement (93%). Bevacizumab appears to be relatively well tolerated, offering a non-invasive therapeutic option for children with NF2 suffering from progressive vestibular schwannomas and hearing loss.

Stereotactic Radiosurgery for Vestibular Schwannoma - A Case-Based Practice Guide from the Radiosurgery Society.

Vestibular schwannomas (VS) are the most common benign intracranial nerve sheath tumors. Surgery and radiotherapy - particularly stereotactic radiosurgery (SRS) - are the primary treatment options. SRS is the dominant treatment for small- and medium-sized VS and selected larger tumors due to its excellent local control rates and favorable safety profile compared to surgery. However, careful treatment planning is essential, taking into account patient preferences, tumor location and size, symptoms, and anticipated treatment-related toxicity. Four clinical VS scenarios have been selected to illustrate the use of SRS, including a unilateral, small intracanalicular VS, a large VS with cystic components, reirradiation with SRS after local tumor recurrence, and bilateral VS in the setting of neurofibromatosis type 2-related schwannomatosis. SRS is an effective and safe treatment modality for the majority of VS cases, requiring careful treatment planning and a thorough understanding of potential limitations and challenges. This case-based practice guide aims to provide a concise overview of the treatment of VS with SRS. We present and discuss four different clinical scenarios of VS to illustrate the pitfalls and best practice recommendations.

Angiotensin-Receptor Blockers Prevent Vestibular Schwannoma-Associated Hearing Loss.

Vestibular schwannoma (VS) tumors typically present with sensorineural hearing loss (SNHL). Losartan has recently demonstrated prevention of tumor-associated SNHL in a mouse model of VS through suppression of inflammatory and pro-fibrotic factors, and the current study investigates this association in humans. This is a retrospective study of patients with unilateral VS and hypertension followed with sequential audiometry at a tertiary referral hospital from January 1994 to June 2023. Patients were stratified into subgroups by anti-hypertensive medication class. SNHL progression was assessed using Kaplan-Meier analysis to account for variable follow-up times. Two hundred thirty-six patients were identified with diagnosis of both VS and hypertension, and with sequential audiometry. Of these, 186 were taking anti-hypertensive therapy at the time of initial VS diagnosis, and 23 were taking losartan or another angiotensin receptor blocker (ARB). Patients taking an ARB were both more likely to have normal baseline hearing and no progressive hearing loss with 36.5 total patient-years of follow-up. Patients taking other anti-hypertensives all showed expected declines in hearing consistent with natural history of VS tumors. This study represents the first statistically significant association between ARB intake and hearing preservation in a real-world VS patient population. Significant confounding factors, such as concomitant hypertension in these patients, could still cloud the full effect of ARB medications' interaction with SNHL progression. Given that ARBs are well tolerated and safe, the results advocate for a prospective clinical trial to validate this effect.

Relationship between nonserviceable hearing and auditory brainstem response in patients with vestibular schwannoma.

The interpretation of ABR results in patients with vestibular schwannoma is often unclear. We investigated the correlation between serviceable hearing in patients with vestibular schwannoma (VS) and factors including auditory brainstem response (ABR) at their initial presentation. We retrospectively analyzed initial magnetic resonance imaging findings, Gardner-Robertson (G&R) classification, ABR, and related data from 72 patients with VS who visited our institution between February 2017 and January 2023. Factors affecting hearing thresholds and nonserviceable hearing were examined. Univariate analysis revealed a significant association between nonserviceable hearing and Koos stage 4, ABR Ⅴ-wave negative, and tumor diameter ≥21.5 mm. In a multivariate analysis, ABR Ⅴ-wave negative was independently associated with nonserviceable hearing. In the present single-center, retrospective sample population, inadequate Ⅴ-waves in the ABR were independently associated with nonserviceable hearing. The findings are useful in explaining serviceable hearing to patients with VS.

Comparing the Accuracy and Reliability of ABC/2 and Planimetry for Vestibular Schwannoma Volume Assessment.

Vestibular schwannoma (VS) is a common intracranial tumor that affects patients' quality of life. Reliable imaging techniques for tumor volume assessment are essential for guiding management decisions. The study aimed to compare the ABC/2 method to the gold standard planimetry method for volumetric assessment of VS. A retrospective review was conducted on patients with VS diagnosed between 2007 and 2022 at Yale New Haven Hospital. Both ABC/2 and planimetry methods were used for tumor volume assessment, and their correlations were evaluated. Among 140 patients, the mean tumor volumes using the planimetry and ABC/2 methods were 1307.99 ± 142.13 and 1482.76 ± 165.75 mm3, respectively. A strong correlation was observed between the methods (r = 0.99, p < 0.0001). For patients who underwent follow-up scans, the ABC/2 method accurately detected tumor volume changes over time. Subgroup analysis based on tumor size also displayed a significant positive correlation across all size categories. The ABC/2 method demonstrates a high correlation with the planimetry method for VS volume assessment and can be a reliable, less time-intensive alternative in clinical settings. However, it generally overestimates tumor volume compared to planimetry. Subgroup-specific correction formulae were provided to enhance the accuracy of ABC/2-derived measurements. Future studies may explore the integration of these methods for improved clinical decision making.

Management of vestibular schwannoma during pregnancy: A systematic review.

This systematic review evaluates the management strategies for vestibular schwannoma (acoustic neuroma) during pregnancy, a rare but significant clinical condition, by synthesizing findings from case reports. A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases. Relevant case reports were included based on predefined inclusion and exclusion criteria. Data were extracted on patient demographics, tumor characteristics, clinical symptoms, management strategies, and outcomes. Thirty-seven cases were included, with a mean patient age of 28.72 years and a mean gestational age at diagnosis of 26.63 weeks. Hearing loss was the most common symptom (92.3%), followed by facial numbness (53.8%) and headache (41%). Tumor sizes ranged from 2.0 to 6.5 cm, with larger tumors associated with increased neurological symptoms. Surgical intervention was performed post-delivery in 78.9% of cases, while 21.1% underwent surgery during pregnancy. Seizures showed a statistically significant difference with the timing of surgery, with one case occurring during pregnancy and none post-delivery (p = 0.05). Most cases were managed conservatively, with surgery deferred until postpartum unless neurological decline or tumor growth warranted earlier intervention. The management of vestibular schwannoma during pregnancy requires a multidisciplinary approach, balancing maternal and fetal health. Conservative management is generally preferred, with surgical intervention reserved for cases with significant symptoms. Hormonal changes during pregnancy may exacerbate tumor growth, underscoring the need for early diagnosis and careful monitoring. Further research is needed to optimize management guidelines and improve outcomes.

Facial Nerve Outcomes following Subtotal, Near-Total, and Total Vestibular Schwannoma Resection: A Retrospective Analysis of the British Skull Base Society National Vestibular Schwannoma Database

Facial Nerve Outcomes following Subtotal, Near-Total, and Total Vestibular Schwannoma Resection: A Retrospective Analysis of the British Skull Base Society National Vestibular Schwannoma Database

Higher Risk of Facial Nerve Function Decrement after Radiosurgery in Vestibular Schwannomas with Prior Surgical Resection

Higher Risk of Facial Nerve Function Decrement after Radiosurgery in Vestibular Schwannomas with Prior Surgical Resection

The Relationship between Pregnancy and Vestibular Schwannoma: A Historically Ignored Aspect of Tumor Management

The Relationship between Pregnancy and Vestibular Schwannoma: A Historically Ignored Aspect of Tumor Management

Association between Vestibular Schwannoma, Meningioma, and Breast Cancer: A Two-Patient Case Study

Association between Vestibular Schwannoma, Meningioma, and Breast Cancer: A Two-Patient Case Study

Timing of Intervention and Adverse Outcomes in Acoustic Schwannomas with Hearing Loss: A Retrospective Study

Timing of Intervention and Adverse Outcomes in Acoustic Schwannomas with Hearing Loss: A Retrospective Study

Comparing Outcomes of Solo Neurosurgical Versus Multidisciplinary Approaches in Retrosigmoid Resection of Vestibular Schwannomas

Comparing Outcomes of Solo Neurosurgical Versus Multidisciplinary Approaches in Retrosigmoid Resection of Vestibular Schwannomas

Facial Nerve and Hearing Preservation after Surgery to Resection Vestibular Schwannomas after Stereotactic Radiosurgery Failure with Gamma Knife: A Systematic Review and Meta-Analysis

Facial Nerve and Hearing Preservation after Surgery to Resection Vestibular Schwannomas after Stereotactic Radiosurgery Failure with Gamma Knife: A Systematic Review and Meta-Analysis

Continuous Facial Nerve Monitoring with Direct Ball-Typed Electrode Stimulation During the Vestibular Schwannoma Surgery

Continuous Facial Nerve Monitoring with Direct Ball-Typed Electrode Stimulation During the Vestibular Schwannoma Surgery

Automated Operative Workflow Recognition in Vestibular Schwannoma Resection: Development and Preclinical Evaluation of a Deep Learning Neural Network (Ideal Stage 0)

Automated Operative Workflow Recognition in Vestibular Schwannoma Resection: Development and Preclinical Evaluation of a Deep Learning Neural Network (Ideal Stage 0)

Principles of Subperineurial Dissection Technique: A Potential Balance between Cranial Nerve Preservation and Extent of Resection in Koos Grade IV Vestibular Schwannomas

Principles of Subperineurial Dissection Technique: A Potential Balance between Cranial Nerve Preservation and Extent of Resection in Koos Grade IV Vestibular Schwannomas

Vestibular Schwannoma Management Paradigm Shift: Has Less Than Total Resection Had An Impact on the Need for Further Treatment and Facial Nerve Outcomes?

Vestibular Schwannoma Management Paradigm Shift: Has Less Than Total Resection Had An Impact on the Need for Further Treatment and Facial Nerve Outcomes?