Unilateral Vestibular Schwannoma Research Articles

Vestibular Assessment with the vHIT and Skull Vibration-Induced Nystagmus Test in Patients with Nonprogressive Vestibular Schwannoma.

Background: Our primary objective was to monitor nonprogressive unilateral vestibular schwannomas (VSs) to assess the efficiency of rapid bedside examinations, such as the video head impulse test (vHIT) and skull vibration-induced nystagmus test (SVINT), in identifying vestibular damage. Methods: An observational study was conducted from March 2021 to March 2022 on all adult patients (>18 years old) with a confirmed nonprogressive VS (no active treatment). The SVINT (using a 100 Hz vibrator with two (SVINT2) or three (SVINT3) stimulation locations) and vHIT (for the six semicircular canals (SCCs)) were performed on all patients. The asymmetry of function between the vestibules was considered significant when the gain asymmetry was greater than 0.1. Rapid and repeatable assessment of VSs using two- and three-stimulation SVINT plus vHIT was performed to quantify intervestibular asymmetry. Results: SVINT3 and SVINT2 triggered VIN in 40% (24/60) and 65% (39/60) of patients, respectively. There was significant asymmetry in the vestibulo-ocular reflex (VOR), as shown by a VS-side gain < healthy-side gain in 58% (35/60) of the patients. Among the patients with significant gain asymmetry between the two vestibules according to the vHIT (VS-side gain < healthy-side gain), the proportion of patients expressing vestibular symptomatology was significantly greater than that of patients without any symptoms [67% (29/43) vs. 35% (6/17), respectively; p = 0.047]. Conclusions: The SVINT2 can be combined with the vHIT to form an interesting screening tool for revealing vestibular asymmetry. This work revealed the superiority of mastoid stimulation over vertex stimulation for SVINT in patients with unilateral vestibular loss.

Predictive factors of tinnitus after vestibular schwannoma surgery: a case-control study

BackgroundTinnitus is very common in patients with vestibular schwannoma (VS). We analyzed the related factors of tinnitus after surgery.MethodsOne hundred seventy-three patients diagnosed with unilateral VS operated via the retrosigmoid approach were included in the study. All patients underwent relevant examinations and completed the THI scale before surgery and 6 months after surgery. The prognosis of tinnitus was evaluated according to the changes in THI.ResultsOf the 129 preoperative tinnitus patients, postoperative tinnitus resolved in 12.4%, improved in 29.5%, remained unchanged in 28.6%, and worsened in 29.5%. 18.2% of 44 patients without preoperative tinnitus appeared new-onset tinnitus postoperatively. Thirty-six patients never had tinnitus. Patients with smaller tumor sizes (≤ 3 cm) were more likely to experience preoperative tinnitus. Younger patients and those with serviceable hearing preoperatively were more likely to report their tinnitus unchanged or worsened. A new onset of postoperative tinnitus in the preoperative non-tinnitus group was found in better preoperative hearing function.ConclusionsIn this study, 70% of patients had persistent tinnitus after vestibular schwannoma resection. The prognosis of tinnitus was influenced by age and preoperative hearing function. Tinnitus is a bothersome symptom and is often underestimated by doctors. Assessment of tinnitus is mandatory during the management of vestibular schwannoma.

Transcanal transpromontorial approach for vestibular schwannoma: experience of a single center.

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. 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 46.7months. We achieved gross total resection of the lesion in all cases, confirmed on the first follow-up MRI at least 6months 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. 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.

Hearing Outcomes from Gamma Knife Treatment for Intracanalicular Vestibular Schwannomas with Good Initial Hearing.

Background: The objective of this study was to describe the long-term hearing outcomes of gamma knife treatment for unilateral progressing vestibular schwannomas (VS) presenting with good initial hearing using audiologic data. Methods: A retrospective review was performed between 2010 and 2020 to select patients with progressing unilateral VS and good hearing (AAO-HNS class A) treated with stereotactic gamma knife surgery (GKS). Their audiograms were analyzed along with treatment metrics and patient data. Results: Hearing outcomes with a median follow-up of 5 years post-treatment showed statistically significant loss of serviceable hearing: 34.1% of patients maintained good hearing (AAO-HNS class A), and 56.1% maintained serviceable hearing (AAO-HNS class A and B). Non-hearing outcomes are favorable with excellent tumor control and low facial nerve morbidity. Conclusions: Hearing declines over time in intracanalicular VS treated with GKS, with a significant loss of serviceable hearing after 5 years. The mean cochlear dose and the presence of cochlear aperture obliteration by the tumor are the main statistically significant factors involved in the hearing outcomes.

An External Validation Study for Automated Segmentation of Vestibular Schwannoma.

To validate how an automated model for vestibular schwannoma (VS) segmentation developed on an external homogeneous dataset performs when applied to internal heterogeneous data. The external dataset comprised 242 patients with previously untreated, sporadic unilateral VS undergoing Gamma Knife radiosurgery, with homogeneous magnetic resonance imaging (MRI) scans. The internal dataset comprised 10 patients from our institution, with heterogeneous MRI scans. An automated VS segmentation model was developed on the external dataset. The model was tested on the internal dataset. Dice score, which measures agreement between ground truth and predicted segmentations. When applied to the internal patient scans, the automated model achieved a mean Dice score of 61% across all 10 images. There were three tumors that were not detected. These tumors were 0.01 ml on average (SD = 0.00 ml). The mean Dice score for the seven tumors that were detected was 87% (SD = 14%). There was one outlier with Dice of 55%-on further review of this scan, it was discovered that hyperintense petrous bone had been included in the tumor segmentation. We show that an automated segmentation model developed using a restrictive set of siloed institutional data can be successfully adapted for data from different imaging systems and patient populations. This is an important step toward the validation of automated VS segmentation. However, there are significant shortcomings that likely reflect limitations of the data used to train the model. Further validation is needed to make automated segmentation for VS generalizable.

Non-occlusive hydrocephalus after radiosurgery for vestibular schwannomas

Stereotactic radiosurgery has firmly entered the arsenal of methods for treating vestibular schwannomas along with traditional surgical removal, providing high control of tumor growth and a low level of functional complications. Meanwhile, there is evidence of a possible relationship between the irradiation performed and the subsequent development of non-occlusive hydrocephalus. Purpose: to retrospectively assess the current level of development of hydrocephalus after stereotactic radiosurgery for vestibular schwannomas. Materials and methods: of 541 patients who received treatment with the Gamma Knife for unilateral vestibular schwannoma, 456 (84.3%) patients initially had no signs of non-occlusive hydrocephalus (group 1), while in 85 (15.7%) patients, MRI signs of internal non-occlusive hydrocephalus were revealed at the time of radiosurgery (group 2), of whom in 1 case VP shunting had previously been performed. In all cases, non-occlusive hydrocephalus at the time of SRS had a compensated course without clinical manifestations. Results: after radiosurgery, the development of de novo non-occlusive hydrocephalus in 7 (1.5%) patients from group 1 and its progression in 11 (12.9%) patients from group 2 were noted. The overall incidence of non-occlusive hydrocephalus after radiosurgery was 3.3%. Ventriculoperitoneal shunting was required in 3 cases in group 1 and 7 cases in group 2 due to the occurrence of neurological symptoms (1.8%). Conclusion: In some cases, radiosurgery can lead to decompensation of existing non-occlusive hydrocephalus, but it rarely occurs de novo. The asymptomatic course of non-occlusive hydrocephalus allows for SRS, as the risk of decompensation with subsequent need for VP shunting is low. Patients with non-occlusive hydrocephalus before SRS require more careful monitoring with assessment of neurological status and control MRI.

Hearing preservation after stereotactic radiosurgery for sporadic intracanalicular vestibular schwannomas classified as Koos grade 1.

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. 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. The median age was 55 years old. The median tumor volume was 0.089 cm3 , 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 cm3 , 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. 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.

Stereotactic Radiosurgery for Vestibular Schwannoma With Radiographic Brainstem Compression.

The safety of single-treatment stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) with radiographic evidence of brainstem compression but without motor deficit is controversial. Data on linear accelerator (linac)-based SRS in this setting are scarce. We address this with an outcomes report from an unselected series of patients with VS with radiographic brainstem compression treated with linac SRS. We included 139 patients with unilateral VS (any size) with radiographic brainstem compression (all without serious brainstem neurological deficits). The SRS prescription dose was 12.5Gy (single fraction) using 6MV linac-produced photon beams, delivered with a multiple arc technique. Inclusion criteria required at least 1 year of radiographic follow-up with magnetic resonance imaging. The primary endpoint was freedom from serious brainstem toxicity (≥grade 3 Common Terminology Criteria for Adverse Events v5); the secondary was freedom from enlargement (tumor progression or any requiring intervention). We assessed serious cranial nerve complications, excluding hearing loss, defined as Common Terminology Criteria for Adverse Events v5 grade 3 toxicity. Median magnetic resonance imaging follow-up time was 5 years, and median tumor size was 2.5cm in greatest axial dimension and 5ml in volume. The median brainstem D0.03ml=12.6Gy and median brainstem V10Gy=0.4ml. At 5 years, the actuarial freedom from serious brainstem toxicity was 100%, and freedom from tumor enlargement (requiring surgery and/or due to progression) was 90%. Severe facial nerve damage in patients without tumor enlargement was 0.9%. Linac-based SRS, as delivered in our series for VS with radiographic brainstem compression, is safe and effective.

RADT-22. STEREOTACTIC RADIOSURGERY FOR VESTIBULAR SCHWANNOMA WITH RADIOGRAPHIC BRAINSTEM COMPRESSION

Abstract BACKGROUND The safety of single treatment stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) with radiographic evidence of brainstem compression- but without motor deficit- is controversial. Data on linac-based SRS in this setting are scarce. We address this deficit in the literature with a report of outcome of an unselected series of patients with VS with radiographic brainstem compression treated with linac SRS our institution. METHODS We included patients with unilateral VS of any size with radiographic brainstem compression at the time of SRS. All patients were without serious brainstem neurologic deficits at the time of SRS. The SRS prescription dose was 12.5 Gy in a single fraction using 6MV photon beams produced by a linear accelerator and delivered with a multiple arc technique. Inclusion in this study required at least 1 year of radiographic follow-up with magnetic resonance imaging (MRI). The primary endpoint was freedom from serious brainstem toxicity (CTCAEv5 grade &amp;gt;3); secondary endpoint was freedom from tumor enlargement considered to represent tumor progression, or any type of enlargement requiring surgical intervention. We also assessed serious cranial nerve complications, excluding hearing loss, defined as CTCAEv5 grade 3 toxicity. RESULTS Among 139 patients, the median MRI follow-up time was 5 years and the median tumor size was 2.5 cm greatest axial dimension and 5cc in volume. The median brainstem D0.03cc = 12.6 Gy, and the median brainstem V10Gy = 0.4cc. At 5 years, the actuarial freedom from serious brainstem toxicity was 100% (zero cases), and freedom from tumor enlargement, either requiring surgery or due to progression, was 90%. The rate of grade 3 facial nerve damage in patients without tumor enlargement was 0.9% (1/113). CONCLUSION Linac-based SRS as delivered in our series for VS with radiographic brainstem compression is safe and effective.

Identification of Follow-Up Markers for Rehabilitation Management in Patients with Vestibular Schwannoma.

This study delves into the absence of prognostic or predictive markers to guide rehabilitation in patients afflicted with vestibular schwannomas. The objective is to analyze the reweighting of subjective and instrumental indicators following surgery, at 7 days and 1 month postoperatively. This retrospective cohort encompasses 32 patients who underwent unilateral vestibular schwannoma surgery at the Marseille University Hospital between 2014 and 2019. Variations in 54 indicators and their adherence to available norms are calculated. After 1 month, one-third of patients do not regain the norm for all indicators. However, the rates of variation unveil specific responses linked to a preoperative error signal, stemming from years of tumor adaptation. This adaptation is reflected in a postoperative visual or proprioceptive preference for certain patients. Further studies are needed to clarify error signals according to lesion types. The approach based on variations in normative indicators appears relevant for post-surgical monitoring and physiotherapy.

P11.62.A GENDER-RELATED DIFFERENCES IN PATIENTS CHARACTERISTICS, AND TREATMENT OUTCOME IN A COMPARATIVE STUDY OF MICROSURGERY AND RADIOSURGERY OF VESTIBULAR SCHWANNOMA

Abstract BACKGROUND Gender-related differences in patients with sporadic, unilateral vestibular schwannoma (VS) are poorly investigated so far. In studies focusing on natural history, tumor growth was described to be indifferent in either sex. However, it remains unclear whether patient’s sex affects the treatment response to stereotactic radiosurgery (SRS) or microsurgical resection (SURGERY). This study elucidates sex-related differences in VS care. MATERIAL AND METHODS This is a retrospective multi-center cohort study. Data was retrospectively collected from two large centers involved in the treatment of vestibular schwannomas for patients between 2005 und 2011 to enable long-term follow-up (FU). Tumor size was classified by Koos Classification. Previously treated VS and patients with Neurofibromatosis were excluded. Clinical state was reported by House and Brackmann (H&amp;B) and Gardner-Robertson (G&amp;R) scale (with H&amp;B&amp;lt;3 and G&amp;R 1-2 considered as good outcome), and Recurrence-free-survival (RFS) was assessed radiographically by contrast-enhanced MR imaging. Data on VS-associated symptoms like trigeminal affection, tinnitus, and vertigo/imbalance were also collected. RESULTS The study population included N=901 patients, who were treated in both centers. N=502 (56%) VS patients were female and N=399 (44%) were male. At time of treatment, women (56 years SD±13.50) were significantly older in age then men (53 years SD±13.80) (p=0.001). Tumor size, cystic morphology, intracanalicular extension, provided care (SRS, SURGERY), treatment related complications, and extent of surgical resection were insignificant in both gender-groups. The incidence of relevant preoperative vertigo was higher in women (67%) then in men (55%) (p=0.002). Pre- and postoperative facial function, hearing loss, and trigeminal symptoms were similar in both groups. Overall incidence of recurrence was insignificant (p=0.106). However, the in subgroups, tumor control with SRS was significantly worse in women compared to men (p=0.035). CONCLUSION Provided Care, functional outcome and peri-interventional morbidity were the same in either sex. Relevant vertigo was significantly more often present in women. The incidence of recurrence is higher in women with VS, when treated with SRS compared to men, although tumor characteristics were similar. Additional research is needed to elucidate gender-related difference in tumor biology affecting the response to VS treatment.

OS09.7.A THE ROLE OF MICROSURGERY IN THE FIRST LINE TREATMENT OF VESTIBULAR SCHWANNOMA: IT IS ALL ABOUT THE ODDS

Abstract BACKGROUND Given the risk for a deterioration of facial function (FDR), first-line (1stline) microsurgery (MS) is discouraged in vestibular schwannoma (VS). In contrast, 1stline radiosurgery (SRS) preserves facial function but has a higher recurrence rate (RR). As salvage VS surgery is very challenging, it could be reasonable to accept a slightly increased FDR of 1stline MS in favor of the lower RR. The aim of the present study was to determine the FDR and RR values of salvage surgery and to calculate the break-even point of MS in the 1stline VS treatment. MATERIAL AND METHODS This retrospective study analyzed all patients with unilateral VS undergoing microsurgery between 03/2008 and 10/2021 (n=1470). We identified patient with 2ndline MS after previous MS (MS-MS) or radiosurgery (SRS-MS) as well as patients with 3rdline MS (MS-SRS-MS). After reviewing patients’ clinical and imaging data, we determined FDR and RR for each cohort. This data was compared to a 1stline MS cohort (CTRL) with a follow-up of at least 10 years (n=572). A mathematical prediction model (MPM) was applied to calculate the odds ratio (OR) of different treatment strategies (i.e., MS-MS, SRS-MS, MS-SRS-MS) depending on different FDR and RR values. RESULTS We identified 48 patients with 2ndline and 11 patients with 3rdline MS after failed MS/SRS. Time to recurrence in relation to the initial treatment was shortest in SRS-MS (35±34 mo) compared to MS-MS (128±179 mo) and MS-SRS-MS (38±17 mo). These patients had a significant worse preoperative facial function than CTRL patients. Extent-of-resection (EOR) was diminished in 2ndline (79% and 75%) compared to 1stline MS (97%). Both the FDR and RR were significantly increased in MS-MS (FDR:17%, RR:14%) and SRS-MS (FDR:45%, RR:5%) compared to CTRL (FDR:12%, RR:4%). Notably, MS-SRS-MS was associated with the highest FDR (60%) while having the lowest GTR rate (54%). MPM indicated that FDR&amp;lt;15% and RR&amp;lt;5% justify a 1stline MS. In the present cohort, these criteria were met for Koos 1-3 tumors (FDR:0-7%, RR:0-3%). CONCLUSION Recurrent VS surgeries fare much worse considering FDR, EOR and RR than first-line surgeries. Hence, reducing the RR of the first-line VS treatment is required. In smaller VS, the surgical oncofunctional outcome can reach the break-even point favoring microsurgery over radiosurgery as first-line treatment option. However, in situations with high FDR (e.g., large or cystic VS) a more conservative surgical approach might be beneficial.

The added value of the artificial intelligence patient-reported experience measure (AI-PREM tool) in clinical practise: Deployment in a vestibular schwannoma care pathway

ObjectivesPatient-reported experience measures (PREMs) can be used for the improvement of quality of care. In this study, the outcome of an open-ended question PREM combined with computer-assisted analysis is compared to the outcome of a closed-ended PREM questionnaire. MethodsThis survey study assessed the outcome of the open-ended questionnaire PREM and a close-ended question PREM of patients with unilateral vestibular schwannoma in a tertiary vestibular schwannoma expert centre. ResultsThe open-ended questions PREM, consisting of five questions, was completed by 507 participants and resulted in 1508 positive and 171 negative comments, categorised into 27 clusters. The close-ended questions PREM results were mainly positive (overall experience graded as 8/10), but did not identify specific action points. Patients who gave high overall scores (>8) on the close-ended question provided points for improvement in the open-ended question PREM, which would have been missed using the close-ended questions only. ConclusionsCompared to the close-ended question PREM, the open-ended question PREM provides more detailed and specific information about the patient experience in the vestibular schwannoma care pathway. InnovationAutomated analysis of feedback with the open-ended question PREM revealed relevant insights and identified topics for targeted quality improvement, whereas the close-ended PREM did not.

Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma

Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically. To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma. Randomized clinical trial of 100 patients with a newly diagnosed (<6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. Participants were enrolled at the Norwegian National Unit for Vestibular Schwannoma from October 28, 2014, through October 3, 2017; 4-year follow-up ended on October 20, 2021. Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires. The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications. Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P = .002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed. Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed. ClinicalTrials.gov Identifier: NCT02249572.

The comparable tumour microenvironment in sporadic and NF2-related schwannomatosis vestibular schwannoma.

Bilateral vestibular schwannoma is the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with a lifetime of surgical interventions, radiotherapy and off-label use of the anti-angiogenic drug bevacizumab. Unilateral vestibular schwannoma develops sporadically in non-NF2-related schwannomatosis patients for which there are no drug treatment options available. Tumour-infiltrating immune cells such as macrophages and T-cells correlate with increased vestibular schwannoma growth, which is suggested to be similar in sporadic and NF2-related schwannomatosis tumours. However, differences between NF2-related schwannomatosis and the more common sporadic disease include NF2-related schwannomatosis patients presenting an increased number of tumours, multiple tumour types and younger age at diagnosis. A comparison of the tumour microenvironment in sporadic and NF2-related schwannomatosis tumours is therefore required to underpin the development of immunotherapeutic targets, identify the possibility of extrapolating ex vivo data from sporadic vestibular schwannoma to NF2-related schwannomatosis and help inform clinical trial design with the feasibility of co-recruiting sporadic and NF2-related schwannomatosis patients. This study drew together bulk transcriptomic data from three published Affymetrix microarray datasets to compare the gene expression profiles of sporadic and NF2-related schwannomatosis vestibular schwannoma and subsequently deconvolved to predict the abundances of distinct tumour immune microenvironment populations. Data were validated using quantitative PCR and Hyperion imaging mass cytometry. Comparative bioinformatic analyses revealed close similarities in NF2-related schwannomatosis and sporadic vestibular schwannoma tumours across the three datasets. Significant inflammatory markers and signalling pathways were closely matched in NF2-related schwannomatosis and sporadic vestibular schwannoma, relating to the proliferation of macrophages, angiogenesis and inflammation. Bulk transcriptomic and imaging mass cytometry data identified macrophages as the most abundant immune population in vestibular schwannoma, comprising one-third of the cell mass in both NF2-related schwannomatosis and sporadic tumours. Importantly, there were no robust significant differences in signalling pathways, gene expression, cell type abundance or imaging mass cytometry staining between NF2-related schwannomatosis and sporadic vestibular schwannoma. These data indicate strong similarities in the tumour immune microenvironment of NF2-related schwannomatosis and sporadic vestibular schwannoma.

Recurrences and progression following microsurgery of vestibular schwannoma.

The treatment approach of vestibular schwannoma (VS) has seen a change in recent years, with a trend away from radical surgery towards preservation of cranial nerve function. A recent study reported recurrences as long as 20 years after complete removal of VS. To report the risk of recurrence and progression in our patient population the authors retrospectively reviewed outcomes of patients. Cases with unilateral VS who had undergone primary microsurgery via retrosigmoidal approach between 1995 and 2021 were investigated. Complete tumor removal was defined as gross total resection (GTR), a capsular remnant was categorized as near total resection (NTR) and residual tumor was designated as subtotal resection (STR). The primary endpoint was radiological recurrence-free survival. 386 patients fulfilled the inclusion criteria of the study and were evaluated. GTR was achieved in 284 patients (73.6%), NTR was achieved in 63 patients (10.1%) and STR was present in 39 patients (16.3%). A total of 28 patients experienced recurrences with significant differences in the three subgroups. The strongest predictor of recurrence was the extent of resection, with patients who underwent STR having an almost 10-fold higher risk of recurrence and patients who had undergone NTR having an almost 3-fold higher risk than those treated with GTR. More than 20% of recurrences (6/28) occured after more than 5 years. The degree of resection is an important guide to the interval of follow-up, but long-term follow-up should be considered also in the case of GTR. The majority of recurrences occurs after 3-5 years. Nevertheless, a follow-up of at least 10 years should be carried out.

Vestibular dysfunction in neurofibromatosis type 2-related schwannomatosis.

Neurofibromatosis type 2-related schwannomatosis is a genetic disorder characterized by neurologic tumours, most typically vestibular schwannomas that originate on the vestibulo-cochlear nerve(s). Although vestibular symptoms can be disabling, vestibular function has never been carefully analysed in neurofibromatosis type 2-related schwannomatosis. Furthermore, chemotherapy (e.g. bevacizumab) can reduce tumour volume and improve hearing in neurofibromatosis type 2-related schwannomatosis, but nothing is known about its vestibular effects. In this report, we studied the three primary vestibular-mediated behaviours (eye movements, motion perception and balance), clinical vestibular disability (dizziness and ataxia), and imaging and hearing in eight untreated patients with neurofibromatosis type 2-related schwannomatosis and compared their results with normal subjects and patients with sporadic, unilateral vestibular schwannoma tumours. We also examined how bevacizumab affected two patients with neurofibromatosis type 2-related schwannomatosis. Vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis degraded vestibular precision (inverse of variability, reflecting a reduced central signal-to-noise ratio) but not vestibular accuracy (amplitude relative to ideal amplitude, reflecting the central signal magnitude) and caused clinical disability. Bevacizumab improved vestibular precision and clinical disability in both patients with neurofibromatosis type 2-related schwannomatosis but did not affect vestibular accuracy. These results demonstrate that vestibular schwannoma tumours in our neurofibromatosis type 2-related schwannomatosis population degrade the central vestibular signal-to-noise ratio, while bevacizumab improves the signal-to-noise ratio, changes that can be explained mechanistically by the addition (schwannoma) and suppression (bevacizumab) of afferent neural noise.

Pseudoprogression of Vestibular Schwannoma after Stereotactic Radiosurgery with Cyberknife®: Proposal for New Response Criteria

(1) Background: Transient increase in volume of vestibular schwannomas (VS) after stereotactic radiosurgery (SRS) is common and complicates differentiation between treatment-related changes (pseudoprogression, PP) and tumor recurrence (progressive disease, PD). (2) Methods: Patients with unilateral VS (n = 63) underwent single fraction robotic-guided SRS. Volume changes were classified according to existing RANO criteria. A new response type, PP, with a >20% transient increase in volume was defined and divided into early (within the first 12 months) and late (>12 months) occurrence. (3) Results: The median age was 56 (range: 20-82) years, the median initial tumor volume was 1.5 (range: 0.1-8.6) cm3. The median radiological and clinical follow-up time was 66 (range: 24-103) months. Partial response was observed in 36% (n = 23), stable disease in 35% (n = 22) and PP in 29% (n = 18) of patients. The latter occurred early (16%, n = 10) or late (13%, n = 8). Using these criteria, no case of PD was observed. (4) Conclusion: Any volume increase after SRS for vs. assumed to be PD turned out to be early or late PP. Therefore, we propose modifying RANO criteria for SRS of VS, which may affect the management of vs. during follow-up in favor of further observation.

The characteristics of brain structural remodeling in patients with unilateral vestibular schwannoma.

Brain structural remodeling alters related brain function. However, few studies have assessed morphological alterations of unilateral vestibular schwannoma (VS) patients. Therefore, this study examined the characteristics of brain structural remodeling in unilateral VS patients. We recruited 39 patients with unilateral VS (19 left, 20 right) and 24 matched normal controls (NCs). We obtained brain structural imaging data using 3T T1-weighted anatomical and diffusion tensor imaging scans. Then, we evaluated both gray and white matter (WM) changes using FreeSurfer software and tract-based spatial statistics, respectively. Furthermore, we constructed a structural covariance network to assess brain structural network properties and the connectivity strength between brain regions. Compared with NCs, VS patients showed cortical thickening in non-auditory areas (e.g., the left precuneus), especially left VS patients, along with reduced cortical thickness in the right superior temporal gyrus (auditory areas). VS patients also showed increased fractional anisotropy in extensive non-auditory-related WM (e.g., the superior longitudinal fasciculus), especially right VS patients. Both left and right VS patients showed increased small-worldness (more efficient information transfer). Left VS patients had a single reduced-connectivity subnetwork in contralateral temporal regions (right-side auditory areas), but increased connectivity between some non-auditory regions (e.g., left precuneus and left temporal pole). VS patients exhibited greater morphological alterations in non-auditory than auditory areas, with structural reductions seen in related auditory areas and a compensatory increase in non-auditory areas. Left and right VS patients show differential patterns of brain structural remodeling. These findings provide a new perspective on the treatment and postoperative rehabilitation of VS.

Atypical functional hierarchy contributed to the tinnitus symptoms in patients with vestibular schwannoma.

Tinnitus is frequently found in patients with vestibular schwannoma (VS), but its underlying mechanisms are currently unclear. Both preoperative (VS pre ) and postoperative (VS post ) functional MR images were collected from 32 patients with unilateral VS and matched healthy controls (HCs). Connectome gradients were generated for the identification of altered regions and perturbed gradient distances. Tinnitus measurements were conducted for predictive analysis with neuroimaging-genetic integration analysis. There were 56.25% of preoperative patients and 65.63% of postoperative patients suffering from ipsilateral tinnitus, respectively. No relevant factors were identified including basic demographics info, hearing performances, tumor features, and surgical approaches. Functional gradient analysis confirmed atypical functional features of visual areas in VS pre were rescued after tumor resection, while the gradient performance in the postcentral gyrus continues to maintain (VS post vs. HC : P = 0.016). The gradient features of the postcentral gyrus were not only significantly decreased in patients with tinnitus (P FDR = 0.022), but also significantly correlated with tinnitus handicap inventory (THI) score (r = -0.30, P = 0.013), THI level (r = -0.31, P = 0.010), and visual analog scale (VAS) rating (r = -0.31, P = 0.0093), which could be used to predict VAS rating in the linear model. Neuropathophysiological features linked to the tinnitus gradient framework were linked to Ribosome dysfunction and oxidative phosphorylation. Altered functional plasticity in the central nervous system is involved in the maintenance of VS tinnitus.