Improved Recovery after Vestibular Schwannoma Excision with Intratympanic Gentamicin Prehabilitation.

OBJECTIVE: Translabyrinthine excision of a vestibular schwannoma is associated with acute vestibular failure. Preoperative intratympanic gentamicin (ITG) injections can improve objective balance function after surgery but its clinical benefits remain to be established. METHODS: Adult patients undergoing translabyrinthine removal of a vestibular schwannoma between January 2014 and February 2018 underwent preoperative vestibular function testing. Patients were divided in to 3 groups, those with vestibular function (VF) who received ITG injections, those with VF but did not receive ITG and those with no VF. Groups were compared according to degree of vertigo, length of stay, time to unassisted mobilization, and postoperative anti-emetic consumption. RESULTS: Forty six patients had ITG injections (Group 1), 7 had residual VF but refused treatment (Group 2), 21 had no VF (Group 3). Group 1 had a significant improvement in vertigo over time whereas groups 2 and 3 did not. There was a statistically significant 70% decrease in time to independent mobilization between Group 1 and other groups and a 19% decrease in length of stay in Group 1 compared to other groups although this did not reach statistical significance. Two patients had injection-related complications. Group 1 used less anti-emetics than other groups but this was not statistically significant. CONCLUSION: Preoperative intratympanic gentamicin injection with vestibular rehabilitation exercises is associated with less postoperative vertigo and earlier postoperative mobilization. There was reduced duration of hospitalization and decreased consumption of anti-emetic but not significantly so possibly because of low numbers of patients in the no treatment group. LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.

Changes in audiovestibular handicap following treatment of vestibular schwannomas.

OBJECTIVE: This study aimed to assess degree of audiovestibular handicap in patients with vestibular schwannoma. METHODS: Audiovestibular handicap was assessed using the Hearing Handicap Inventory, Tinnitus Handicap Inventory and Dizziness Handicap Inventory. Patients completed questionnaires at presentation and at least one year following treatment with microsurgery, stereotactic radiosurgery or observation. Changes in audiovestibular handicap and factors affecting audiovestibular handicap were assessed. RESULTS: All handicap scores increased at follow up, but not significantly. The Tinnitus Handicap Inventory and Dizziness Handicap Inventory scores predicted tinnitus and dizziness respectively. The Hearing Handicap Inventory was not predictive of hearing loss. Age predicted Tinnitus Handicap Inventory score and microsurgery was associated with a deterioration in Dizziness Handicap Inventory score. CONCLUSION: Audiovestibular handicap is common in patients with vestibular schwannoma, with 75 per cent having some degree of handicap in at least one inventory. The overall burden of handicap was, however, low. The increased audiovestibular handicap over time was not statistically significant, irrespective of treatment modality.

Generating Operative Workflows for Vestibular Schwannoma Resection: A Two-Stage Delphi's Consensus in Collaboration with the British Skull Base Society. Part 2: The Translabyrinthine Approach.

Objective An operative workflow systematically compartmentalizes operations into hierarchal components of phases, steps, instrument, technique errors, and event errors. Operative workflow provides a foundation for education, training, and understanding of surgical variation. In this Part 2, we present a codified operative workflow for the translabyrinthine approach to vestibular schwannoma resection. Methods A mixed-method consensus process of literature review, small-group Delphi's consensus, followed by a national Delphi's consensus was performed in collaboration with British Skull Base Society (BSBS). Each Delphi's round was repeated until data saturation and over 90% consensus was reached. Results Seventeen consultant skull base surgeons (nine neurosurgeons and eight ENT [ear, nose, and throat]) with median of 13.9 years of experience (interquartile range: 18.1 years) of independent practice participated. There was a 100% response rate across both the Delphi rounds. The translabyrinthine approach had the following five phases and 57 unique steps: Phase 1, approach and exposure; Phase 2, mastoidectomy; Phase 3, internal auditory canal and dural opening; Phase 4, tumor debulking and excision; and Phase 5, closure. Conclusion We present Part 2 of a national, multicenter, consensus-derived, codified operative workflow for the translabyrinthine approach to vestibular schwannomas. The five phases contain the operative, steps, instruments, technique errors, and event errors. The codified translabyrinthine approach presented in this manuscript can serve as foundational research for future work, such as the application of artificial intelligence to vestibular schwannoma resection and comparative surgical research.

Generating Operative Workflows for Vestibular Schwannoma Resection: A Two-Stage Delphi's Consensus in Collaboration with the British Skull Base Society. Part 1: The Retrosigmoid Approach.

Objective An operative workflow systematically compartmentalizes operations into hierarchal components of phases, steps, instrument, technique errors, and event errors. Operative workflow provides a foundation for education, training, and understanding of surgical variation. In this Part 1, we present a codified operative workflow for the retrosigmoid approach to vestibular schwannoma resection. Methods A mixed-method consensus process of literature review, small-group Delphi's consensus, followed by a national Delphi's consensus, was performed in collaboration with British Skull Base Society (BSBS). Each Delphi's round was repeated until data saturation and over 90% consensus was reached. Results Eighteen consultant skull base surgeons (10 neurosurgeons and 8 ENT [ear, nose, and throat]) with median 17.9 years of experience (interquartile range: 17.5 years) of independent practice participated. There was a 100% response rate across both Delphi's rounds. The operative workflow for the retrosigmoid approach contained three phases and 40 unique steps as follows: phase 1, approach and exposure; phase 2, tumor debulking and excision; phase 3, closure. For the retrosigmoid approach, technique, and event error for each operative step was also described. Conclusion We present Part 1 of a national, multicenter, consensus-derived, codified operative workflow for the retrosigmoid approach to vestibular schwannomas that encompasses phases, steps, instruments, technique errors, and event errors. The codified retrosigmoid approach presented in this manuscript can serve as foundational research for future work, such as operative workflow analysis or neurosurgical simulation and education.

The clinical, genetic, and immune landscape of meningioma in patients with NF2-schwannomatosis.

NF2-schwannomatosis is the most common genetic predisposition syndrome associated with meningioma. Meningioma in NF2-schwannomatosis is a major source of morbidity and mortality. This is due to accumulative tumor burden in patients with synchronous schwannomas and ependymomas, sometimes including complex collision tumors. Balancing the impact of multiple interventions against the natural history of various index tumors, and the ongoing risk of de novo tumors over an individual's lifetime makes decision-making complex. The management of any given individual meningioma is often different from a comparable sporadic tumor. There is typically a greater emphasis on conservative management and tolerating growth until a risk boundary is reached, whereby symptomatic deterioration or higher risk from anticipated future treatment is threatened. Management by high-volume multidisciplinary teams improves quality of life and life expectancy. Surgery remains the mainstay treatment for symptomatic and rapidly enlarging meningioma. Radiotherapy has an important role but carries a higher risk compared to its use in sporadic disease. Whilst bevacizumab is effective in NF2-associated schwannoma and cystic ependymoma, it has no value in the management of meningioma. In this review, we describe the natural history of the disease, underlying genetic, molecular, and immune microenvironment changes, current management paradigms, and potential therapeutic targets.

The experience of auditory implant recipients undergoing magnetic resonance imaging: Factors associated with pain.

OBJECTIVE: Many patients with cochlear implants (CI) and auditory brainstem implants (ABI) require magnetic resonance imaging (MRI) following implantation. This study explores the patient experience of MRI, identifying factors associated with pain, and the effect of interventions designed to enhance comfort and safety. METHODS: A prospective observational case series from a tertiary referral unit. Tight head bandaging ± local anaesthetic injection (devices with non-MRI-compatible magnets) or observation alone (implants with MRI-compatible magnets) were employed for 1.5 T MRI of consecutive adult patients with CI or ABI without magnet removal. Pain was recorded via visual analogue scale (1 = no pain, 5 = extreme pain) at three time points; (1) baseline, (2) head bandage applied (3) during scanning. Patient age, device type, body area imaged and total scan time were recorded as variables, alongside adverse events. RESULTS: Data were collected for 227 MRI scans (34 patients with ABI, 32 with CI). In patients managed with bandaging, pain score after bandaging but prior to scanning (median 2.2) did not differ from pain during scanning (2.1), but both were significantly higher than baseline (1.4, both P ≤ 0.001). Scanning areas other than the head/cervical spine was associated with higher pain scores (P = 0.036). Pain during MRI differed between different manufacturers implants (P ≤ 0.001). Adverse events occurred in 8/227 scans (3.5%), none occurring with devices containing an MRI-compatible magnet. CONCLUSION: MRI scanning with auditory implant magnets in situ is safe and well tolerated by patients.

Intraoperative diagnosis of facial schwannomas: a multicenter summation of clinical experience, preoperative avoidance, and intraoperative management protocol.

OBJECTIVE: Preoperative differentiation of facial nerve schwannoma (FNS) from vestibular schwannoma (VS) can be challenging, and failure to differentiate between these two pathologies can result in potentially avoidable facial nerve injury. This study presents the combined experience of two high-volume centers in the management of intraoperatively diagnosed FNSs. The authors highlight clinical and imaging features that can distinguish FNS from VS and provide an algorithm to help manage intraoperatively diagnosed FNS. METHODS: Operative records of 1484 presumed sporadic VS resections between January 2012 and December 2021 were reviewed, and patients with intraoperatively diagnosed FNSs were identified. Clinical data and preoperative imaging were retrospectively reviewed for features suggestive of FNS, and factors associated with good postoperative facial nerve function (House-Brackmann [HB] grade ≤ 2) were identified. A preoperative imaging protocol for suspected VS and recommendations for surgical decision-making following an intraoperative FNS diagnosis were created. RESULTS: Nineteen patients (1.3%) with FNSs were identified. All patients had normal facial motor function preoperatively. In 12 patients (63%), preoperative imaging demonstrated no features suggestive of FNS, with the remainder showing subtle enhancement of the geniculate/labyrinthine facial segment, widening/erosion of the fallopian canal, or multiple tumor nodules in retrospect. Eleven (57.9%) of the 19 patients underwent a retrosigmoid craniotomy, and in the remaining patients, a translabyrinthine (n = 6) or transotic (n = 2) approach was used. Following FNS diagnosis, 6 (32%) of the tumors underwent gross-total resection (GTR) and cable nerve grafting, 6 (32%) underwent subtotal resection (STR) and bony decompression of the meatal facial nerve segment, and 7 (36%) underwent bony decompression only. All patients undergoing subtotal debulking or bony decompression exhibited normal postoperative facial function (HB grade I). At the last clinical follow-up, patients who underwent GTR with a facial nerve graft had HB grade III (3 of 6 patients) or IV facial function. Tumor recurrence/regrowth occurred in 3 patients (16%), all of whom had been treated with either bony decompression or STR. CONCLUSIONS: Intraoperative diagnosis of an FNS during a presumed VS resection is rare, but its incidence can be reduced further by maintaining a high index of suspicion and undertaking further imaging in patients with atypical clinical or imaging features. If an intraoperative diagnosis does occur, conservative surgical management with bony decompression of the facial nerve only is recommended, unless there is significant mass effect on surrounding structures.

Genome-wide association analysis identifies a susceptibility locus for sporadic vestibular schwannoma at 9p21.

Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants. To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 × 10-13, odds ratio = 0.67, allele frequency = 0.52). 9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis.

Long-Term Outcomes of the Electrically Unresponsive, Anatomically Intact Facial Nerve Following Vestibular Schwannoma Surgery.

Objective The study aimed to determine long-term outcomes in patients with intraoperative electrical conduction block in an anatomically intact facial nerve (FN). Methods Single center retrospective review of prospectively collected database of all vestibular schwannoma surgeries between January 1, 2008 and August 25, 2015. Operative notes were reviewed and patients with anatomically intact FNs, but complete conduction block at the end of surgery were included for analysis. Results In total, 371 patients had vestibular schwannoma surgery of which 18 met inclusion criteria. Mean follow-up was 34.28 months and average tumor size was 28.00 mm. Seventeen patients had House-Brackmann Grade VI facial palsy immediately postoperatively and one patient was grade V. At 1 year, three patients remained grade VI (17%), two improved to grade V (11%), seven to grade IV (39%), six to grade III (33%), and one patient to grade II (6%). On extended follow-up, five patients (28%) had additional 1 to 2 score improvement in facial function. Subset analysis revealed no correlation of tumor size, vascularity, adherence to nerve, operative approach, extent of resection, splaying of FN, and recurrent tumor or sporadic tumors to the extent of FN recovery. Conclusion Intraoperative conduction block does not condemn a patient to permanent FN palsy. There is potential for a degree of recovery comparable with those undergoing nerve grafting. Our data do not clearly support a policy of same-surgery or early-postoperative primary nerve grafting in the event of a complete conduction block, and instead we favor monitoring for recovery in an anatomically intact nerve.

Beyond Antoni: A Surgeon's Guide to the Vestibular Schwannoma Microenvironment.

Introduction Vestibular schwannomas (VS) are histologically benign tumors arising from cranial nerve VIII. Far from a homogenous proliferation of Schwann cells, mounting evidence has highlighted the complex nature of the inflammatory microenvironment in these tumors. Methods A review of the literature pertaining to inflammation, inflammatory molecular pathways, and immune-related therapeutic targets in VS was performed. Relevant studies published up to June 2020 were identified based on a literature search in the PubMed and MEDLINE databases and the findings were synthesized into a concise narrative review of the topic. Results The VS microenvironment is characterized by a dense infiltrate of inflammatory cells, particularly macrophages. Significantly higher levels of immune cell infiltration are observed in growing versus static tumors, and there is a demonstrable interplay between inflammation and angiogenesis in growing VS. While further mechanistic studies are required to ascertain the exact role of inflammation in angiogenesis, tumor growth, and Schwann cell control, we are beginning to understand the key molecular pathways driving this inflammatory microenvironment, and how these processes can be monitored and targeted in vivo . Conclusion Observational research has revealed a complex and heterogeneous tumor microenvironment in VS. The functional landscape and roles of macrophages and other immune cells in the VS inflammatory infiltrate are, however, yet to be established. The antiangiogenic drug bevacizumab has shown the efficacy of targeted molecular therapies in VS and there is hope that agents targeting another major component of the VS microenvironment, inflammation, will also find a place in their future management.

The utility of the exoscope compared to the operating microscope in simulated temporal bone surgery.

OBJECTIVE: To objectively assess the utility of an exoscope during simulated otological surgery. DESIGN: Cohort study. SETTING: Tertiary referral otolaryngology centre. PARTICIPANTS: Seven experienced otologists undertook simulated temporal bone surgery on plastic temporal bones using the Zeiss Kinevo microscope with both a microscope and exoscope facility. OUTCOME MEASURES: The utility of microscope and exoscope was compared using a Likert scale from 1 to 10 with and without PPE. Attributes assessed included image quality, depth perception, adequacy of view, exoscope positioning, surgeon comfort, surgeon safety and adequacy of image and protection for assistants and observers. RESULTS: The exoscope in 3D mode performed as well as or better than the microscope for image quality, field of view and manoeuvrability. It outperformed the microscope for compatibility with PPE, surgeon comfort and assistant/observer experience. It scored almost as highly as the microscope for depth perception. CONCLUSION: There is likely to be a learning curve but this initial assessment of the exoscope shows significant potential as an alternative to the operating microscope in otological surgery but with the advantage of allowing the use of appropriate PPE and better ergonomics for both surgeon and assistant/observer.

Disease course of neurofibromatosis type 2: a 30-year follow-up study of 353 patients seen at a single institution.

BACKGROUND: Limited data exist on the disease course of neurofibromatosis type 2 (NF2) to guide clinical trial design. METHODS: A prospective database of patients meeting NF2 diagnostic criteria, reviewed between 1990 and 2020, was evaluated. Follow-up to first vestibular schwannoma (VS) intervention and death was assessed by univariate analysis and stratified by age at onset, era referred, and inheritance type. Interventions for NF2-related tumors were assessed. Cox regression was performed to determine the relationship between individual factors from time of diagnosis to NF2-related death. RESULTS: Three hundred and fifty-three patients were evaluated. During 4643.1 follow-up years from diagnosis to censoring, 60 patients (17.0%) died. The annual mean number of patients undergoing VS surgery or radiotherapy declined, from 4.66 and 1.65, respectively, per 100 NF2 patients in 1990-1999 to 2.11 and 1.01 in 2010-2020, as the number receiving bevacizumab increased (2.51 per 100 NF2 patients in 2010-2020). Five patients stopped bevacizumab to remove growing meningioma or spinal schwannoma. 153/353 (43.3%) had at least one neurosurgical intervention/radiation treatment within 5 years of diagnosis. Patients asymptomatic at diagnosis had longer time to intervention and better survival compared to those presenting with symptoms. Those symptomatically presenting <16 and >40 years had poorer overall survival than those presenting at 26-39 years (P = .03 and P = .02, respectively) but those presenting between 16 and 39 had shorter time to VS intervention. Individuals with de novo constitutional variants had worse survival than those with de novo mosaic or inherited disease (P = .004). CONCLUSION: Understanding disease course improves prognostication, allowing for better-informed decisions about care.

The microenvironment in sporadic and neurofibromatosis type II-related vestibular schwannoma: the same tumor or different? A comparative imaging and neuropathology study.

OBJECTIVE: Inflammation and angiogenesis may play a role in the growth of sporadic and neurofibromatosis type 2 (NF2)-related vestibular schwannoma (VS). The similarities in microvascular and inflammatory microenvironment have not been investigated. The authors sought to compare the tumor microenvironment (TME) in sporadic and NF2-related VSs using a combined imaging and tissue analysis approach. METHODS: Diffusion MRI and high-temporal-resolution dynamic contrast-enhanced (DCE) MRI data sets were prospectively acquired in 20 NF2-related and 24 size-matched sporadic VSs. Diffusion metrics (mean diffusivity, fractional anisotropy) and DCE-MRI-derived microvascular biomarkers (transfer constant [Ktrans], fractional plasma volume, tissue extravascular-extracellular space [ve], longitudinal relaxation rate, tumoral blood flow) were compared across both VS groups, and regression analysis was used to evaluate the effect of tumor size, pretreatment tumor growth rate, and tumor NF2 status (sporadic vs NF2-related) on each imaging parameter. Tissues from 17 imaged sporadic VSs and a separate cohort of 12 NF2-related VSs were examined with immunohistochemistry markers for vessels (CD31), vessel permeability (fibrinogen), and macrophage density (Iba1). The expression of vascular endothelial growth factor (VEGF) and VEGF receptor 1 was evaluated using immunohistochemistry, Western blotting, and double immunofluorescence. RESULTS: Imaging data demonstrated that DCE-MRI-derived microvascular characteristics were similar in sporadic and NF2-related VSs. Ktrans (p < 0.001), ve (p ≤ 0.004), and tumoral free water content (p ≤ 0.003) increased with increasing tumor size and pretreatment tumor growth rate. Regression analysis demonstrated that with the exception of mean diffusivity (p < 0.001), NF2 status had no statistically significant effect on any of the imaging parameters or the observed relationship between the imaging parameters and tumor size (p > 0.05). Tissue analysis confirmed the imaging metrics among resected sporadic VSs and demonstrated that across all VSs studied, there was a close association between vascularity and Iba1+ macrophage density (r = 0.55, p = 0.002). VEGF was expressed by Iba1+ macrophages. CONCLUSIONS: The authors present the first in vivo comparative study of microvascular and inflammatory characteristics in sporadic and NF2-related VSs. The imaging and tissue analysis results indicate that inflammation is a key contributor to TME and should be viewed as a therapeutic target in both VS groups.

Incidence of mosaicism in 1055 de novo NF2 cases: much higher than previous estimates with high utility of next-generation sequencing.

PURPOSE: To evaluate the incidence of mosaicism in de novo neurofibromatosis 2 (NF2). METHODS: Patients fulfilling NF2 criteria, but with no known affected family member from a previous generation (n = 1055), were tested for NF2 variants in lymphocyte DNA and where available tumor DNA. The proportion of individuals with a proven or presumed mosaic NF2 variant was assessed and allele frequencies of identified variants evaluated using next-generation sequencing. RESULTS: The rate of proven/presumed mosaicism was 232/1055 (22.0%). However, nonmosaic heterozygous pathogenic variants were only identified in 387/1055 (36.7%). When variant detection rates in second generation nonmosaics were applied to de novo cases, we assessed the overall probable mosaicism rate to be 59.7%. This rate differed by age from 21.7% in those presenting with bilateral vestibular schwannoma <20 years to 80.7% in those aged ≥60 years. A mosaic variant was detected in all parents of affected children with a single-nucleotide pathogenic NF2 variant. CONCLUSION: This study has identified a very high probable mosaicism rate in de novo NF2, probably making NF2 the condition with the highest expressed rate of mosaicism in de novo dominant disease that is nonlethal in heterozygote form. Risks to offspring are small and probably correlate with variant allele frequency detected in blood.

Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing.

PURPOSE: We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). METHODS: Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis. RESULTS: There was no evidence for usefulness of old criteria "glioma" or "neurofibroma." "Ependymoma" had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%. CONCLUSIONS: The present study confirms important deficiencies in NF2 diagnostic criteria. The term "glioma" should be dropped and replaced by "ependymoma." Similarly "neurofibroma" should be removed. Dropping "sibling" from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS.

Familial unilateral vestibular schwannoma is rarely caused by inherited variants in the NF2 gene.

OBJECTIVES/HYPOTHESIS: Unilateral vestibular schwannoma (VS) occurs with a lifetime risk of around 1 in 1,000 and is due to inactivation of the NF2 gene, either somatically or from a constitutional mutation. It has been postulated that familial occurrence of unilateral VS occurs more frequently than by chance, but no causal mechanism has been confirmed. STUDY DESIGN: Retrospective database analysis. METHODS: The likelihood of chance occurrence of unilateral VS, or occurring in the context of neurofibromatosis type 2 (NF2), was assessed using national UK audit data and data from the national NF2 database. Families with familial unilateral VS (occurrence in first- and second-degree relatives) were assessed for constitutional NF2 and LZTR1 genetic variants, and where possible the tumor was also analyzed. RESULTS: Approximately 1,000 cases of unilateral VS occurred annually in the United Kingdom between 2013 and 2016. Of these, 2.5 may be expected to have a first-degree relative who had previously developed a unilateral VS. The likelihood of this occurring in NF2 was considered to be as low as 0.05 annually. None of 28 families with familial unilateral VS had a constitutional NF2 intragenic variant, and in nine cases where the VS was analyzed, both mutational events in NF2 were identified and excluded from the germline. Only three variants of uncertain significance were found in LZTR1. CONCLUSIONS: Familial occurrence of unilateral VS is very unlikely to be due to a constitutional NF2 or definitely pathogenic LZTR1 variant. The occurrence of unilateral VS in two or more first-degree relatives is likely due to chance. This phenomenon may well increase in clinical practice with increasing use of cranial magnetic resonance imaging in older patients. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:967-973, 2019.

Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma.

BACKGROUND: Inflammation is hypothesized to be a key event in the growth of sporadic vestibular schwannoma (VS). In this study we sought to investigate the relationship between inflammation and tumor growth in vivo using the PET tracer 11C-(R)-PK11195 and dynamic contrast enhanced (DCE) MRI derived vascular biomarkers. METHODS: Nineteen patients with sporadic VS (8 static, 7 growing, and 4 shrinking tumors) underwent prospective imaging with dynamic 11C-(R)-PK11195 PET and a comprehensive MR protocol, including high temporal resolution DCE-MRI in 15 patients. An intertumor comparison of 11C-(R)-PK11195 binding potential (BPND) and DCE-MRI derived vascular biomarkers (Ktrans, vp, ve) across the 3 different tumor growth cohorts was undertaken. Tissue of 8 tumors was examined with immunohistochemistry markers for inflammation (Iba1), neoplastic cells (S-100 protein), vessels (CD31), the PK11195 target translocator protein (TSPO), fibrinogen for vascular permeability, and proliferation (Ki-67). Results were correlated with PET and DCE-MRI data. RESULTS: Compared with static tumors, growing VS displayed significantly higher mean 11C-(R)-PK11195 BPND (-0.07 vs 0.47, P = 0.020), and higher mean tumor Ktrans (0.06 vs 0.14, P = 0.004). Immunohistochemistry confirmed the imaging findings and demonstrated that TSPO is predominantly expressed in macrophages. Within growing VS, macrophages rather than tumor cells accounted for the majority of proliferating cells. CONCLUSION: We present the first in vivo imaging evidence of increased inflammation within growing sporadic VS. Our results demonstrate that 11C-(R)-PK11195 specific binding and DCE-MRI derived parameters can be used as imaging biomarkers of inflammation and vascular permeability in this tumor group.

Schwannomatosis: a genetic and epidemiological study.

OBJECTIVES: Schwannomatosis is a dominantly inherited condition predisposing to schwannomas of mainly spinal and peripheral nerves with some diagnostic overlap with neurofibromatosis-2 (NF2), but the underlying epidemiology is poorly understood. We present the birth incidence and prevalence allowing for overlap with NF2. METHODS: Schwannomatosis and NF2 cases were ascertained from the Manchester region of England (population=4.8 million) and from across the UK. Point prevalence and birth incidence were calculated from regional birth statistics. Genetic analysis was also performed on NF2, LZTR1 and SMARCB1 on blood and tumour DNA samples when available. RESULTS: Regional prevalence for schwannomatosis and NF2 were 1 in 126 315 and 50 500, respectively, with calculated birth incidences of 1 in 68 956 and 1 in 27 956. Mosaic NF2 causes a substantial overlap with schwannomatosis resulting in the misdiagnosis of at least 9% of schwannomatosis cases. LZTR1-associated schwannomatosis also causes a small number of cases that are misdiagnosed with NF2 (1%-2%), due to the occurrence of a unilateral vestibular schwannoma. Patients with schwannomatosis had lower numbers of non-vestibular cranial schwannomas, but more peripheral and spinal nerve schwannomas with pain as a predominant presenting symptom. Life expectancy was significantly better in schwannomatosis (mean age at death 76.9) compared with NF2 (mean age at death 66.2; p=0.004). CONCLUSIONS: Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.

Management of Cochlear Nerve Hypoplasia and Aplasia.

Approximately 2% of congenital profound deafness cases are due to cochlear nerve (CN) deficiency. MRI is essential to confirm if the nerve is deficient, but because of limitations with resolution, especially when the internal auditory canal is narrowed, it is often unable to distinguish between hypoplasia and aplasia. A full audiometric test battery should always be performed, even if the MRI suggests CN aplasia, as there will sometimes be evidence of audition. Electrically evoked auditory brainstem response testing can be carried out transtympanically via the round window or using an intracochlear test electrode to help determine the status of the CN. If any test suggests the presence of a CN, then cochlear implantation (CI) should be considered. Children should be followed up closely with audiometric, electrophysiological and language assessments to determine the benefits. They may initially show benefit but fail to progress. CI results are variable and often result in poor outcomes with Categories of Auditory Perception scores of <5. Auditory brainstem implantation (ABI) can be considered when CI is contraindicated or fails to provide adequate benefit. This may provide better outcomes, but this form of surgery has greater risks and future device replacement (in case of device failure) may be complicated. Careful patient selection is required when considering ABI as significant learning difficulties make programming extremely challenging. Patients should be given the option of CI first and then ABI. A small minority of patients presenting late (around 2-3 years of age) may be candidates for simultaneous CI and ABI.