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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.

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.

Background: Radiation treatment of benign tumors in tumor predisposition syndromes is controversial, but short-term studies from treatment centers suggest safety despite apparent radiation-associated malignancy being reported. We determined whether radiation treatment in NF2-related schwannomatosis patients is associated with increased rates of subsequent malignancy (M)/malignant progression (MP)., Methods: All UK patients with NF2 were eligible if they had a clinical/molecular diagnosis. Cases were NF2 patients treated with radiation for benign tumors. Controls were matched for treatment location with surgical/medical treatments based on age and year of treatment. Prospective data collection began in 1990 with addition of retrospective cases in 1969. Kaplan-Meier analysis was performed for malignancy incidence and survival. Outcomes were central nervous system (CNS) M/MP (2cm annualized diameter growth) and survival from index tumor treatment., Results: In total, 1345 NF2 patients, 266 (133-Male) underwent radiation treatments between 1969 and 2021 with median first radiotherapy age of 32.9 (IQR = 22.4-46.0). Nine subsequent CNS malignancies/MPs were identified in cases with only 4 in 1079 untreated ( P < .001). Lifetime and 20-year CNS M/MP was ~6% in all irradiated patients-(4.9% for vestibular schwannomas [VS] radiotherapy) versus <1% in the non-irradiated population ( P < .001/.01). Controls were well matched for age at NF2 diagnosis and treatment (Males = 133%-50%) and had no M/MP in the CNS post-index tumor treatment ( P = .0016). Thirty-year survival from index tumor treatment was 45.62% (95% CI = 34.0-56.5) for cases and 66.4% (57.3-74.0) for controls ( P = .02), but was nonsignificantly worse for VS radiotherapy., Conclusion: NF2 patients should not be offered radiotherapy as first-line treatment of benign tumors and should be given a frank discussion of the potential 5% excess absolute risk of M/MP., Competing Interests: None other than many of the authors are surgeons, but 4 are oncologists., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: There is evidence that macrophage infiltration in the tumor microenvironment promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab in NF2-associated VS demonstrates the value of therapies targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target., Objective: To characterize the relationship between growth, TAM infiltration, and circulating monocyte chemokines in a large cohort of patients with VS., Methods: Immunostaining for Iba1 (macrophages), CD31 (endothelium), and fibrinogen (permeability) was performed on 101 growing and 19 static sporadic VS. The concentrations of monocyte-specific chemokines were measured in the plasma of 50 patients with growing VS and 25 patients with static VS., Results: The Iba1 + cell count was significantly higher in growing as compared with static VS (592 vs 226/×20 HPF, P =<0.001). Similarly, the CD31 + % surface area was higher in growing VS (2.19% vs 1.32%, P = .01). There was a positive correlation between TAM infiltration and VS growth rate, which persisted after controlling for the effect of tumor volume (aR2 = 0.263, P =<0.001). The plasma concentrations of several monocytic chemokines were higher in patients with growing rather than static VS., Conclusion: There is a strong positive correlation between TAM infiltration and volumetric growth of VS, and this relationship is independent of tumor size. There is a colinear relationship between TAM infiltration and tumor vascularity, implying that inflammation and angiogenesis are interlinked in VS. Chemokines known to induce monocyte chemotaxis are found in higher concentrations in patients with growing VS, suggestive of a potential pathophysiological mechanism., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background  Evidence on hearing outcome measures when assessing hearing preservation following stereotactic radiosurgery (SRS) for adults with vestibular schwannoma (VS) has not previously been collated in a structured review. Objective  The objective of the present study was to perform a scoping review of the evidence regarding the choice of hearing outcomes and other methodological characteristics following SRS for adults with VS. Methods  The protocol was registered in the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses extension guidelines for scoping reviews. A systematic search of five online databases revealed 1,591 studies, 247 of which met the inclusion criteria. Results  The majority of studies ( n  = 213, 86%) were retrospective cohort or case series with the remainder ( n  = 34, 14%) prospective cohort. Pure-tone audiometry and speech intelligibility were included in 222 (90%) and 158 (64%) studies, respectively, often summarized within a classification scheme and lacking procedural details. Fifty-nine (24%) studies included self-report measures. The median duration of follow-up, when reported, was 43 months (interquartile range: 29, 4-150). Conclusion  Evidence on hearing disability after SRS for VS is based on low-quality studies which are inherently susceptible to bias. This review has highlighted an urgent need for a randomized controlled trial assessing hearing outcomes in patients with VS managed with radiosurgery or radiological observation. Similarly, consensus and coproduction of a core outcome set to determine relevant hearing and communication outcome domains is required. This will ensure that patient priorities, including communication abilities in the presence of background noise and reduced participation restrictions, are addressed., Competing Interests: Conflict of Interest I.A. is supported by the NIHR Manchester Biomedical Research Centre, and the Deanship of Scientific Research at the College of Applied Medical Sciences Research Center at King Saud University. K.J.M. reports grants received from NIHR and is supported by the NIHR Manchester Biomedical Research Centre. S.K.L. is supported by the NIHR Manchester Biomedical Research Centre. The services of an Information Specialist and publication fees for Open Access were provided by NIHR Manchester Biomedical Research Centre., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Bilateral vestibular schwannomas (VS) are pathognomonic of neurofibromatosis type 2 (NF2), but the diagnostic criteria also include unilateral VS (UVS) in combination with multiple meningiomas (MM) and other schwannomas, as well as MM without VS., Objective: To investigate the diagnostic value of these criteria and establish the presence of other genetic conditions in patients presenting in this manner., Methods: The Manchester International NF2 database was accessed to obtain information on patients presenting with a UVS and MM or ≥2 nonintradermal schwannomas (NIDS). We gathered data on patients diagnosed with NF2 due to MM without VS and on patients presenting with MM without meeting NF2 criteria. Analysis was performed for pathogenic variants (PVs) in NF2, SMARCE1, SMARCB1, and LZTR1., Results: A total of 31 of 131 patients presenting with a UVS and MM had a nonrefuted diagnosis of NF2 after molecular studies, in comparison with 85 of 96 patients presenting with UVS and ≥2 NIDS (P ≤ .00001). Fifty percent of patients presenting with a UVS and ≥2 NIDS with NF2 developed bilateral VS, compared with only 26% of those who presented with a UVS and MM (P = .0046). In total, 11 of 152 patients presenting with MM without fulfilling NF2 criteria were found to have a PV in SMARCE1, and 7 of 152 were confirmed to have mosaic NF2., Conclusion: Patients presenting with UVS and MM are significantly more likely to have a nonrefuted diagnosis of NF2 than patients presenting with UVS and ≥2 NIDS, but significantly less likely to develop bilateral VS. Seven percent of those presenting with MM without meeting NF2 criteria had PV in SMARCE1, and 5% had mosaic NF2., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objectives: This study seeks the opinions of qualified doctors on what they feel medical students should learn about otolaryngology. It aims to identify both the content deemed relevant and the performance levels for medical students in otolaryngology., Methods: A national survey developed from a content analysis of undergraduate otolaryngology curricula from the UK was undertaken, accompanied by a review of the literature and input from an expert group. Data were collected from a wide range of doctors., Results: Participants felt that graduating students should be able to: recognise, assess and initiate management for common and life-threatening acute conditions; take an appropriate patient history; and perform an appropriate examination for the majority of otolaryngology clinical conditions but manage only a select few., Conclusion: This study reports performance levels for otolaryngology topics at an undergraduate level. Participating doctors felt that a higher level of performance should be expected of students treating life-threatening, acute and common otolaryngology conditions.

The authors present the case of a 24-year-old female with neurofibromatosis type 2. Growth of the left vestibular schwannoma and progressive hearing loss prompted the decision to proceed to translabyrinthine resection with cochlear nerve preservation and cochlear implant insertion. Complete resection with preservation of the facial and cochlear nerves was achieved. The patient had grade 1 facial function and was discharged on postoperative day 4 following suturing of a minor CSF leak. This case highlights the feasibility of cochlear nerve preservation and cochlear implant insertion in appropriately selected patients, offering a combination of effective tumor control and hearing rehabilitation. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21122., Competing Interests: Disclosures Dr. Evans reports personal fees from AstraZeneca, outside the submitted work.Dr. Evans reports personal fees from AstraZeneca, outside the submitted work., (© 2021, The Authors.)

Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS). The mechanisms of tumour response are, however, unknown and in this study we sought to evaluate changes in the irradiated VS tumour microenvironment through a multinuclear MRI approach. Five patients with growing sporadic VS underwent a multi-timepoint comprehensive MRI protocol, which included diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE) MRI and a spiral 23 Na-MRI acquisition for total sodium concentration (TSC) quantification. Post-treatment voxelwise changes in TSC, DTI metrics and DCE-MRI derived microvascular biomarkers (K trans , v e and v p ) were evaluated and compared against pre-treatment values. Changes in tumour TSC and microvascular parameters were observable as early as 2 weeks post-treatment, preceding changes in structural imaging. At 6 months post-treatment there were significant voxelwise increases in tumour TSC (p < 0.001) and mean diffusivity (p < 0.001, repeated-measures ANOVA) with marked decreases in tumour microvascular parameters (p < 0.001, repeated-measures ANOVA). This study presents the first in vivo evaluation of alterations in the VS tumour microenvironment following SRS, demonstrating that changes in tumour sodium homeostasis and microvascular parameters can be imaged as early as 2 weeks following treatment. Future studies should seek to investigate these clinically relevant MRI metrics as early biomarkers of SRS response., (© 2021. The Author(s).)

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 Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The COVID-19 pandemic has forced an unprecedented worldwide change in our daily lives, particularly in healthcare. In response to the lockdown measure it has brought on, some deaneries cancelled planned teaching days, while others had delivered remote smaller scale teaching sessions electronically. Due to significant regional variation, the National Association of Program Directors in ENT (NAPDENT) set up a national educational program, matched to the Intercollegiate Surgical Curriculum Program. This is delivered virtually and for free. This pilot survey evaluates participants' learning experience of the first NAPDENT National Otology Training Day, which was held on 20 April 2020 via Zoom. This is a pilot survey evaluating the first online, national educational program delivered by the NAPDENT in the United Kingdom. In the times of the COVID-19 pandemic, our program has rapidly learnt from this initial experience and continues to build on lessons learnt for future editions. It is feasible to augment the national ENT curriculum with a collaborative, online teaching program. Regional buy-in is required to make this work. This modality allows for access to subject experts across the country. Synchronous delivery allows for participant interaction, while an online repository allows for asynchronous viewing when work or personal commitments do not allow live attendance. The key to participant engagement is adequate structure, appropriate breaks and opportunities for interaction. Even once the COVID-19 pandemic has passed, this teaching modality will remain as an opportunity to educate ENT surgeons of the future., (Copyright © 2020. Published by Elsevier Inc.)

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., Competing Interests: Conflict of Interest D.G.E. reports personal fees from Astrazeneca, outside the submitted work. All the other authors report no conflict of interest., (Thieme. All rights reserved.)

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.

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., (© 2018 The Authors. The Laryngoscope published by Wiley Periodicals, Inc. on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Neurofibromatosis type 2 (NF2) is a complex disease characterized by the development of multiple schwannomas, especially vestibular schwannomas, as well as other types of benign tumours including meningioma and spinal ependymoma. Due to its multisystem nature, the management of NF2 requires a multidisciplinary approach. In England, the delivery of care for NF2 patients has been centralized to four-"hub" centres in Manchester, Cambridge, Oxford and London each having associated "spoke" centres. Each centre has a core multidisciplinary team consisting of genetics, otolaryngology, neurosurgery, paediatrics, neurology, audiology, radiology, psychology, physiotherapy, specialist nurses and administrative staff. In addition, the core team has access to plastic surgery, ophthalmology, peripheral nerve surgery and adult and paediatric oncology. There are weekly multidisciplinary clinics each with six to eight patients. Each patient is discussed during a team meeting and the management decisions that are made are then discussed with the patients. All patients are reviewed at least annually and have annual head magnetic resonance imaging (MRI) and three yearly spinal MRI. Annual audiological assessment is performed. Cochlear implantation and auditory brainstem implantation are offered if indicated. Surgery, stereotactic radiosurgery and bevacizumab therapy are available for the management of intracranial and spinal tumours. The integration of the service in England has provided significant benefits to patient care and, in the long term, will provide robust patient outcome data that will provide an evidence base to assist in optimizing management of patients with NF2., (Copyright © 2016. Published by Elsevier Masson SAS.)

Background: The Manchester criteria for neurofibromatosis type 2 (NF2) include a range of tumors, and gliomas were incorporated in the original description. The gliomas are now widely accepted to be predominantly spinal cord ependymomas., Objective: To determine whether these gliomas include any cases of malignant glioma (WHO grade III and IV) through a database review., Methods: The prospective database consists of 1253 patients with NF2. 1009 are known to be alive at last follow-up., Results: There was a single case of glioblastoma multiforme (GBM; World Health Organization grade IV) in the series and no WHO grade III gliomas. The GBM was in a patient who had previously undergone stereotactic radiosurgery for a vestibular schwannoma., Conclusion: High-grade gliomas are not a feature of NF2 in the unirradiated patient and should be excluded from the diagnostic criteria.

Background: The published literature suggests that malignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in neurofibromatosis type 2 (NF2). A recent review based on incidence data in North America showed that 1 per 1000 cerebellopontine angle nerve sheath tumors were malignant., Objective: To determine whether MPNST occurred spontaneously in NF2 by reviewing our NF2 database., Methods: The prospective database consists of 1253 patients with NF2. One thousand and nine are known to be alive at last follow-up. The presence and laterality/pathology of vestibular schwannoma at diagnosis and last follow-up was sought., Results: There were no cases of spontaneous MPNST with 2114 proven (n = 1150) and presumed benign (n = 964) vestibular schwannomas found. Two patients had developed MPNST (1 presumed) after having previously undergone stereotactic radiosurgery for a vestibular schwannoma., Conclusion: In this series, and from the literature, malignant transformation of a vestibular schwannoma was not a feature of NF2 in the unirradiated patient. NF2 patients should not be told that they have an increased risk of malignant change in a vestibular schwannoma unless they undergo radiation treatment. However, very much larger datasets are required before it can be determined whether there is any association between NF2 and MPNST in the unirradiated patient.

The management of spinal cord ependymomas in Neurofibromatosis Type 2 (NF2) has traditionally been conservative, in contrast to the management of sporadic cases; the assumption being that, in the context of NF2, they did not cause morbidity. With modern management and improved outcome of other NF2 tumours, this assumption, and therefore the lack of role for surgery, has been questioned. To compare the outcome of conservative treatment of spinal ependymomas in NF2 with surgical intervention in selected patients. Retrospective review at two NF2 centers, Manchester, UK and Paris/Lille, France. In Manchester patients were managed conservatively. In France surgery was a treatment option. Inclusion in the study was based on tumor length of greater than 1.5 cm. The primary parameter assessed was acquired neurological deficit measured by the Modified McCormick Outcome Score. 24 patients from Manchester and 46 patients from France were analyzed. From Manchester, 27% of these patients deteriorated during the course of follow-up. This effectively represents the natural history of ependymomas in NF2. Of the surgical cases, 23% deteriorated postoperatively, but only 2/18 (11%) of those operated on in the NF2 specialist centers. Comparison of the two specialist centers Manchester/France showed a significantly improved outcome (P = 0.012, χ 2 test) in the actively surgical center. Spinal ependymomas produce morbidity. Surgery can prevent or improve this in selected cases but can itself can produce morbidity. Surgery should be considered in growing/symptomatic ependymomas, particularly in the absence of overwhelming tumor load where bevacizumab is the preferred option.

A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk. Forty studies using animal models or cell cultures met specified inclusion criteria, most of which were designed to examine the role of heme iron or heterocyclic amines in relation to colon carcinogenesis. Most studies used levels of meat or meat components well in excess of those found in human diets. Although many of the experiments used semi-purified diets designed to mimic the nutrient loads in current westernized diets, most did not include potential biologically active protective compounds present in whole foods. Because of these limitations in the existing literature, there is currently insufficient evidence to confirm a mechanistic link between the intake of red meat as part of a healthy dietary pattern and colorectal cancer risk. Impact statement Current recommendations to reduce colon cancer include the reduction or elimination of red or processed meats. These recommendations are based on data from epidemiological studies conducted among cultures where meat consumption is elevated and consumption of fruits, vegetables, and whole grains are reduced. This review evaluated experimental data exploring the putative mechanisms whereby red or processed meats may contribute to colon cancer. Most studies used levels of meat or meat-derived compounds that were in excess of those in human diets, even in cultures where meat intake is elevated. Experiments where protective dietary compounds were used to mitigate the extreme levels of meat and meat-derived compounds showed protection against colon cancer, with some essentially negating the impact of meat in the diet. It is essential that better-designed studies be conducted that use relevant concentrations of meat or meat-derived compounds in complex diets representative of the foods consumed by humans.

Background: Obese individuals present with an increased inflammatory tone as compared to healthy, normal-weight individuals, which is associated with insulin resistance. One factor hypothesized to contribute to increased inflammation in obese and diabetic states is elevated blood endotoxin levels, a condition known as metabolic endotoxemia. In non-obese and insulin sensitive individuals, circulating endotoxin concentrations fluctuate over the course of the day with elevations in the post-prandial state that return to baseline levels in the post-absorptive state. Evidence suggests that high-fat feeding alters these fluctuations causing endotoxin levels to remain high throughout the day. The effects of alterations in endotoxin levels on glucose metabolism are not clearly understood., Purpose/procedures: The goal of this study was to determine the effects of both short-term and long-term increases in endotoxin (lipopolysaccharide, LPS) of a low magnitude on the glucose tolerance and insulin signaling in a human primary cell line as well as the effects of short-term endotoxin treatments on glucose homeostasis in a C57/Bl6 mouse model. First, we tested the hypothesis that short-term low-dose endotoxin treatments would augment insulin signaling and glycogen synthesis while long-term treatments would be disruptive in the cell culture model. Second, we examined if these short-term low dose treatments of endotoxin would contribute to similar improvements in whole-body glucose homeostasis in a mouse model., Main Findings: Contrary to our initial hypothesis, short-term endotoxin treatment had no effect on insulin signaling or glycogen synthesis, however long-term treatment indeed decreased glycogen synthesis (P<.05). Interestingly, short-term endotoxin treatment resulted in significant improvements in glucose homeostasis in the mouse model (P<.01); which is believed to be at least partly attributed to an inhibitory action of LPS on liver glucose production., Conclusions: This research shows that low-magnitude, short-term changes in LPS can have significant effects on whole body glucose metabolism and this likely occurs through its direct actions on the liver. Additional studies are necessary to understand the mechanisms responsible for altered glucose metabolism in response to low magnitude changes in LPS levels., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: A pneumocele occurs when an aerated cranial cavity pathologically expands; a pneumatocele occurs when air extends from an aerated cavity into adjacent soft tissues forming a secondary cavity. Both pathologies are extremely rare with relation to the mastoid. This paper describes a case of a mastoid pneumocele that caused hypoglossal nerve palsy and an intracranial pneumatocele., Case Report: A 46-year-old man presented, following minor head trauma, with hypoglossal nerve palsy secondary to a fracture through the hypoglossal canal. The fracture occurred as a result of a diffuse temporal bone pneumocele involving bone on both sides of the hypoglossal canal. Further slow expansion of the mastoid pneumocele led to a secondary middle fossa pneumatocele. The patient refused treatment and so has been managed conservatively for more than five years, and he remains well., Conclusion: While most patients with otogenic pneumatoceles have presented acutely in extremis secondary to tension pneumocephalus, our patient has remained largely asymptomatic. Aetiology, clinical features and management options of temporal bone pneumoceles and otogenic pneumatoceles are reviewed.

Objective: To determine the specificity of the current clinical diagnostic criteria for neurofibromatosis type 2 (NF2) relative to the requirement for unilateral vestibular schwannoma (VS) and at least 2 other NF2-related tumors., Methods: We interrogated our Manchester NF2 database, which contained 205 individuals meeting NF2 criteria who initially presented with a unilateral VS. Of these, 83 (40.7%) went on to develop a contralateral VS. We concentrated our genetic analysis on a group of 70 who initially fulfilled NF2 criteria with a unilateral vestibular schwannoma and at least 2 additional nonintradermal schwannomas., Results: Overall, 5/70 (7%) individuals with unilateral VS and at least 2 other schwannomas had a pathogenic or likely pathogenic LZTR1 mutation. Twenty of the 70 subsequently developed bilateral disease. Of the remaining 50, 5 (10%) had a germline LZTR1 mutation, equivalent to the number (n = 5) with a germline NF2 mutation., Conclusions: The most common etiology for unilateral VS and 2 additional NF2-associated tumors in this cohort was mosaic NF2. Germline LZTR1 and germline NF2 mutations were equally common in our cohort. This indicates that LZTR1 must be considered when making a diagnosis of NF2 in the presence of unilateral VS in individuals without a germline NF2 mutation., (© 2016 American Academy of Neurology.)

Objective: To describe the experience of auditory brainstem implantation (ABI) in patients with Neurofibromatosis type 2 (NF2)., Study Design: Retrospective case review., Setting: Tertiary referral centre., Patients: Implanted with a Cochlear ABI22 or ABI24M between 1994 and 2009 because of NF2 disease., Intervention(s): Rehabilitative., Main Outcome Measure(s): Surgical complication rate; audiological outcomes., Results: There were 50 primary ABI insertions in 49 patients, including 16 inserted at the time of first side tumor removal as a sleeper, and two revision repositionings which failed to improve outcome. Postoperatively three patients had cerebrospinal fluid leaks which did not require reoperation, one patient had meningitis, and eleven patients suffered either temporary or permanent lower cranial nerve dysfunction. Twenty-nine patients became full time users; a further 12 patients became non-users. Three patients died while their device was inactive. Five patients retain serviceable contralateral hearing. Audiological open set testing of users showed means of: environmental sounds discrimination 51%; phoneme discrimination: with ABI alone 22%/lip reading (LR) 45%/ABI with LR 65%; sentence testing: with ABI alone 13%/LR 19%/ABI with LR 54%., Conclusions: The majority of patients with NF2 implanted with an ABI find the device a useful aid to communication in conjunction with LR and in recognizing common environmental sounds. A small proportion gain open set discrimination. Almost a third of patients may end up as non-users. There is probably an increased risk of postoperative lower cranial nerve dysfunction so careful preoperative assessment is advised.

In neurofibromatosis type 2 (NF2) bilateral vestibular schwannomas (VS) or their treatment usually results in bilateral hearing loss. Cochlear implantation (CI) was traditionally not used in these patients due to concern that retrocochlear disease would render the implant ineffective. This paper describes the auditory outcomes of CI in 13 patients with NF2 and includes patients with untreated VS and patients undergoing VS removal with cochlear nerve preservation. The non-user rate was 7.7%. Of the active users, median CUNY score was 98%, median BKB score in quiet was 90% and median BKB score in noise was 68%. CI is a viable option in selected patients with NF2.

Objectives: The aim of this study was to quantify the benefit gained from cochlear implantation in pre- or peri-lingually deafened patients who were implanted as adults Methods: This was a retrospective case-control study. Auditory (BKB/CUNY/3AFC/Environmental sounds), quality of life (GBI/HUI3) and cognitive (customized questionnaire) outcomes in 26 late implanted pre- or peri-lingually deafened adults were compared to those of 30 matched post-lingually deafened, traditional cochlear implant users., Results: There was a statistically significant improvement in all scores in the study group following cochlear implantation. BKB scores for cases was 49.8% compared to 83.6% for controls (p=0.037). CUNY scores for cases was 61.7% compared to 90.3% for controls (p=0.022). The 3AFC and environmental sounds scores were also better in controls compared to cases but the difference was not statistically significant. Quality of life scores improved following implantation in cases and controls but the improvement was only statistically significant in the controls. There was a 7.7% non-user rate in the cases. There were no non-users in the control group., Discussion: Early deafened,,late implanted patients can benefit audiologically from cochlear implantation and in this study the improvement in speech discrimination scores was greater than expected perhaps reflecting careful selection of patients. Nevertheless, audiological benefits are limited compared to traditional cochlear implant recipients with the implant acting as an aid to lip reading in most cases., Conclusion: With careful selection of candidates, cochlear implantation is beneficial in early deafened, late implanted patients.

The objective of this study was to describe changes in hearing over time in patients with neurofibromatosis type 2 (NF2) treated conservatively. A retrospective case review was conducted in a tertiary referral centre. Pure tone audiometry, speech discrimination scores, serviceable hearing (American Academy of Otolaryngology class A or B) and measurement of vestibular schwannoma (VS) size on magnetic resonance imaging were evaluated in 56 patients (89 ears) with NF2 with at least one conservatively managed VS. Over a mean follow-up period of 7 years (range 0.8-21 years) pure tone average thresholds increased gradually with a mean annual rate of 1.3 dB for the right ear (p = 0.0003) and 2 dB for the left ear (p = 0.0009). Speech discrimination scores dropped with an average annual rate of 1.3 and 0.34% in the right and left ear, respectively. Patients maintained serviceable hearing for an average of 7.6 years (range 2.7-19.3 years). The average annual VS growth was 0.4 mm without any correlation with hearing loss. There was a correlation between patients' age and pure tone threshold increase (p < 0.05 for both ears). In this selected population of patients with NF2, hearing threshold increases were very slow. In NF2 patients with indolently behaving tumours, serviceable hearing can be maintained for a significant length of time, making conservative management an attractive option.

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.

Background: Neurofibromatosis Type 2 (NF2) is a dominantly inherited tumour syndrome with a phenotype which includes bilateral vestibular (eighth cranial nerve) schwannomas. Conventional thinking suggests that these tumours originate at a single point along the superior division of the eighth nerve., Methods: High resolution MRI was performed in children genetically proven to have NF2. The superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) were visualised along their course with points of tumour origin calculated as a percentage relative to the length of the nerve., Results: Out of 41 patients assessed, 7 patients had no identifiable eighth cranial nerve disease. In 16 patients there was complete filling of the internal auditory meatus by a tumour mass such that its specific neural origin could not be determined. In the remaining 18 cases, 86 discrete separate foci of tumour origin on the SVN or IVN could be identified including 23 tumours on the right SVN, 26 tumours on the right IVN, 18 tumours on the left SVN and 19 tumours on the left IVN., Discussion: This study, examining the origins of vestibular schwannomas in NF2, refutes their origin as being from a single site on the transition zone of the superior division of the vestibular nerve. We hypothesise a relationship between the number of tumour foci, tumour biology and aggressiveness of disease. The development of targeted drug therapies in addition to bevacizumab are therefore essential to improve prognosis and quality of life in patients with NF2 given the shortcomings of surgery and radiation treatments when dealing with the multifocality of the disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aim: To assess the long-term subjective benefits of auditory brainstem implants (ABIs) and investigate the extent to which ABI users perceive it to be a useful device., Methods: Using the Manchester database, all 31 living patients registered as ABI users were identified and sent the ABI performance questionnaire. Data regarding daily duration of use, auditory fatigue, ability to differentiate between speech and environmental sounds, and subjective usefulness of the ABI in different listening conditions were collected. Patients were asked to rate the usefulness of the device in various settings on a scale of 1 (not useful) to 6 (very useful). The mean age at implantation was 33 years (13-73 yr), and the mean follow-up period was 6 years (1.5-15 yr)., Results: Between March 1994 and September 2009, 57 patients underwent ABI insertion. A total of 26 patients were not eligible for inclusion in the study (19 nonusers, 5 deceased, and 2 sleepers). Of the 31 eligible patients identified as ABI users, 23 returned the questionnaire, 1 was excluded as the questionnaire had been completed on his or her behalf, giving a net response rate of 71%. Mean duration of usage per day was 12.62 hours (range, 8-16 h). Seventy-one percent of the patients turned the processor off at one or more points during the day. Differentiation between speech and environment was achieved in 95%, and 70% were able to differentiate between gender and adult and pediatric voices. The ABI was perceived as most beneficial when dealing with a familiar voice in a quiet place, with a median usefulness score of 4, rising to 5 when used in conjunction with lip reading. The ABI was least useful when dealing with an unfamiliar voice in a loud place, with a mean score of 1, rising to 2 when used in conjunction with lip reading. In all environments, combining the ABI with lip reading served to increase usefulness ratings by at least 1 point., Conclusion: This study demonstrates that ABI users make use of their device for at least 12 hours per day on average and obtain considerable subjective benefit in speech discrimination when using the device with familiar speakers in a quiet environment. Benefit is less significant in noise and with an unfamiliar speaker. Lip reading enhances subjective benefit by at least 1 point, and lip reading training may have a role to play in maximizing subjective benefit.

Objective: To present a review of all patients diagnosed with a facial nerve schwannoma (FNS) managed in our center over almost two decades, and suggest guidelines for their classification and management., Study Design: Retrospective case review, Setting: Tertiary referral center, Patients: Twenty-eight patients with a facial nerve schwannoma, Intervention: Conservative or surgical management depending on clinical and radiological features, Main Outcome Measure: Patient demographics, site of tumor, and clinical symptoms, including facial nerve function (House-Brackmann score) at baseline and follow-up. In those managed surgically, operative approach and surgical outcomes were also recorded., Results: Of 28 patients, 16 were male. Mean age at presentation was 46 years. The majority presented with either facial weakness or hearing loss. The internal auditory canal segment of the facial nerve was the most commonly affected (19/28, 68%). Multi-segmental lesions were found in almost half (46%) of patients. Facial weakness was most commonly associated with involvement of the labyrinthine segment (89%). Overall, 16 (57%) patients were managed surgically., Conclusion: FNS may be difficult to distinguish on both clinical and imaging grounds from other cerebellopontine pathologies on the basis of audiovestibular symptoms alone. The presence of facial weakness in combination with imaging findings suggestive of FNS is highly suggestive for FNS. In patients with brainstem compression, rapid tumor growth, or House-Brackmann greater than 4, we suggest a surgical approach based on preoperative audiovestibular status, helping optimize long-term facial function and minimize morbidity. Facial nerve reanimation at the time of primary surgery is preferred.

Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant condition with high spontaneous mutation rate which predisposes to the development of multiple nerve sheath tumours (schwannomas), meningiomas and ependymoma. The cardinal feature and main diagnostic criterion for the diagnosis of NF2 remains the development of bilateral vestibular schwannoma (BVS). With increasing use of MRI screening the possibility of a 'chance' diagnosis of BVS has been mooted with a potential frequency of one in two million people in their lifetime. Until now, however, no evidence for such an event has been published. We aimed to demonstrate that chance occurrence can occur and to estimate its frequency among those with just BVS late in life., Methods: Two vestibular schwannomas from the same patient were DNA sequenced and underwent loss of heterozygosity analysis., Results: We show that a man who developed BVS, at ages 52 and 67 years developed these tumours sporadically by demonstrating that there were no molecular events in common between the two tumours. Furthermore from a database of over 1200 patients with NF2, we have estimated that ~25% of cases of BVS over 50 years and 50% over 70 years of age where no other features of NF2 are present represent a chance occurrence rather than due to an underlying mosaic or constitutional NF2 mutation., Conclusions: Patients presenting with BVS later in life should be appraised of the potential likelihood they may not have NF2 and the resultant further reduction in risks of transmission to offspring., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To determine differences in speech perception outcomes for patients who received a CI422 and a Contour cochlear implant., Study Design: Retrospective case review., Setting: Tertiary referral center., Patients: Thirty-two adults who underwent cochlear implantation., Intervention: Cochlear implantation using a CI422 or Contour device., Main Outcome Measure: Bamford-Kowal-Bench (BKB) speech perception scores at 3 and 9 months after activation., Results: The mean BKB scores at 3 months for the CI422 device were 86.0% in quiet and 55.1% in noise. This compares with 86.0% in quiet and 62.3% in noise for the Contour device. At 9 months, the mean BKB scores were 85.9% in quiet and 67.1% in noise for the CI422 and 90.1% in quiet and 77.6% in noise for the Contour device. There was no statistically significant difference (p > 0.05) between speech perception outcomes at 3 or 9 months., Conclusion: This study suggests that CI422 and Contour electrode both improve speech perception outcomes postoperatively, and there does not appear to be any significant difference in outcome between the two types of devices.

Objective: This study describes our experience of cochlear implantation (CI) with hearing preservation in adolescents. Our aim was to determine if hearing preservation is successful in this population, if the preserved hearing is maintained, and what the potential benefit of preserving hearing in this population is., Patients: Fourteen profoundly deaf adolescents with preservation of low-frequency hearing (125, 250, and 500 Hz)., Intervention: Twelve adolescents had a single-sided CI, and two had bilateral CI. All were having their first implantation, and all patients had hearing preservation surgery (soft surgery)., Main Outcome Measures: Hearing preservation was measured with preoperative and postoperative pure-tone audiograms. Speech audiometry was performed before implantation and at subsequent follow-up appointments., Results: Hearing preservation (measurable hearing thresholds) was achieved in 13 of 14 patients. Average follow-up was 2 years 10 months (range, 4 mo-4 yr 9 mo). Three of 13 patients with initial successful hearing preservation had deterioration of their hearing at subsequent follow-up. The addition of naturally preserved hearing to the cochlear implant improved speech audiometry scores compared with using the implants in isolation., Conclusion: This study demonstrates that residual hearing can be consistently preserved and maintained in adolescents during the short-/medium-term using a soft surgical technique to insert standard-length electrodes. The potential benefit of preserving residual low-frequency hearing seems to be improvement in speech discrimination in challenging hearing conditions, although larger studies are required.

Objective: To determine the indications for, and auditory outcomes following, cochlear reimplantation in adults and investigate factors influencing outcome., Study Design: Retrospective case series., Setting: Cochlear implant program in a tertiary care hospital., Patients: Thirty adults (32 ears) who have undergone cochlear reimplantation in the ipsilateral ear., Intervention(s): Explantation and reimplantation of cochlear implant., Main Outcome Measure(s): Speech discrimination as measured using Bamford-Kowal Bench sentence testing in quiet (BKBq) and noisy (BKBn) environments., Results: Best BKBq improved from 58.5% to 71.4% (p = 0.0242), and BKBn improved from 60.9% to 67.2% (p = 0.826) after reimplantation. Device failure was the most common indication for reimplantation. There was no significant difference in failure rate or outcome between implant manufacturers. The mean time to reimplantation was 4.7 years, and this was not related to auditory outcome. Otosclerosis and Ménière's disease may predispose to a worse auditory outcome after reimplantation., Conclusion: Cochlear reimplantation does not have a detrimental effect on auditory outcomes and in some cases results in improved speech perception.

Objective: To review the postoperative surgical outcomes of cystic vestibular schwannomas (CVSs), especially facial nerve outcomes, and compare these results with those from matched solid vestibular schwannomas (SVS) resected during the same period at a tertiary referral center., Study Design: Retrospective case series., Methods: One hundred thirty-one surgically managed patients with cystic vestibular schwannomas (CVSs) were age, sex, and tumor size matched to 131 surgically managed patients with solid vestibular schwannomas (SVSs). Demographics, tumor morphology, surgical approach, extent of resection, facial and nonfacial complications, and recurrence rates were compared between the 2 groups. Subtotal removal was defined as removal of at least 95% of the tumor., Results: The mean maximal tumor diameter was 2.8 cm for both groups. For CVS, gross total tumor resection (GTR) was achieved in 92 patients (70.2%), and subtotal tumor resection (STR) was achieved in 39 patients (29.8%). Postoperative facial nerve outcomes at 1-year follow-up were good (HB Grade I-III) in 116 (88.5%) of 131 CVS patients. Twenty-three patients developed nonfacial nerve-related complications (17.6%). For SVS, GTR was achieved in 102 patients (77.9%), and STR was achieved in 29 patients (22.1%). Postoperative facial nerve outcomes at 1-year follow-up were good (HB Grade I-III) in 118 (90.1%) of 131 SVS patients. Nonfacial nerve related complications occurred in 14 patients (10.7%). None of the differences in outcome between the 2 groups were statistically significant., Conclusion: The difference in surgical outcomes is minimal between patients with CVS and those with SVS, not reaching statistical significance. We think, with judicious surgical management, similar outcomes can be achieved in cystic tumors and solid tumors.

Objective: To date, only a very limited number of lipomas of the cerebellopontine angle (CPA) have been reported. Our objective was to examine clinical and radiologic features of CPA lipomas and determine the most appropriate management plan., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Patients with CPA lipomas were identified through the skull base multidisciplinary meeting database., Interventions: Radiologic surveillance and clinical assessment., Main Outcome Measures: Tumor growth, assessed through radiologic measurements on serial magnetic resonance imaging, demographics, presenting symptoms, and any correlation between weight gain and lipoma growth were among the examined factors., Results: Of the 15 patients with CPA lipomas, six were female and nine were male, with an average age at presentation of 50.2 years (range, 31.7-76.4 yr) and an average follow-up time of 51.7 months (range, 6-216 mo). The lipomas were unilateral in all cases, nine on the right (60%) and six on the left (40%) side. None of the lipomas increased in size. All patients were treated conservatively. Sensorineural hearing loss was the main presenting symptom (80%) followed by tinnitus (46.7%) and vertigo (20%). None of the patients suffered from facial nerve dysfunction. There was no correlation between weight gain and tumor growth., Conclusion: CPA lipomas can be diagnosed accurately with appropriate magnetic resonance imaging techniques and be managed conservatively with safety. Cochleovestibular are the most common presenting symptoms, whereas facial nerve involvement is rare. CPA lipomas do not tend to grow and can be monitored on a less regular basis.

Objective: To systematically summarise the peer-reviewed literature relating to the aetiology, clinical presentation, investigation and treatment of geniculate neuralgia., Data Sources: Articles published in English between 1932 and 2012, identified using Medline, Embase and Cochrane databases., Methods: The search terms 'geniculate neuralgia', 'nervus intermedius neuralgia', 'facial pain', 'otalgia' and 'neuralgia' were used to identify relevant papers., Results: Fewer than 150 reported cases were published in English between 1932 and 2012. The aetiology of the condition remains unknown, and clinical presentation varies. Non-neuralgic causes of otalgia should always be excluded by a thorough clinical examination, audiological assessment and radiological investigations before making a diagnosis of geniculate neuralgia. Conservative medical treatment is always the first-line therapy. Surgical treatment should be offered if medical treatment fails. The two commonest surgical options are transection of the nervus intermedius, and microvascular decompression of the nerve at the nerve root entry zone of the brainstem. However, extracranial intratemporal division of the cutaneous branches of the facial nerve may offer a safer and similarly effective treatment., Conclusion: The response to medical treatment for this condition varies between individuals. The long-term outcomes of surgery remain unknown because of limited data.

Aim: To present the outcomes of cochlear implantation (CI) in children with auditory neuropathy spectrum disorders (ANSD)., Materials and Methods: The pre- and post-CI hearing outcomes in children with ANSD were retrospectively evaluated. Performance was assessed with categories of auditory performance (CAP) and the Manchester spoken language development scale (MSLDS)., Results: Full data were available in 27 implanted children with ANSD with average age at implantation 35.4 months (range 19-68 months). Nine children were implanted bilaterally, while 13 were bimodal. The pre-CI CAP and MSLDS scores were 2.5 (range 0-5) and 2.5 (range 0-6), while the post-CI scores 5.8 (range 2-9) and 7.7 (range 3-10), respectively., Conclusions: Although the outcome of CI in children with ANSD might vary, it is favourable in most of the cases. CI seems a justified hearing rehabilitation option for children with ANSD and limited benefits from conventional hearing aids.

Objective: To investigate the outcomes from ipsilateral simultaneous or sequential cochlear implantation in patients with neurofibromatosis type 2 (NF2) after vestibular schwannoma removal with cochlear nerve preservation., Study Design: Retrospective case series., Setting: Single tertiary referral NF2 center., Patients: Six patients with NF2., Intervention: Removal of vestibular schwannoma (VS) with preservation of the cochlear nerve and cochlear implantation. Four patients had their surgery via a translabyrinthine approach. Two patients had a retrosigmoid approach. A cochlear implant was inserted at the same time as tumor removal in 4 cases and sequentially in 2 cases., Main Outcome Measures: Surgical and audiometric outcomes using Bamford-Kowal-Bench (BKB) and City of New York University (CUNY) sentence scores., Results: The average age at implantation was 24 years (range, 15-36 yr). Follow-up ranged from 5 to 93 months, with an average of 38 months. All patients had useful hearing in the contralateral ear before surgery. One patient gained no benefit from cochlear implantation and proceeded to have an auditory brainstem implant. Of those that had functional cochlear nerves, the average BKB score in quiet was 64%, BKB score in noise was 42%, and CUNY score with lipreading was 97%. Results varied within the group, but all patients gained significant benefit and continue to use their CI at least intermittantly., Conclusion: The present series demonstrates that in selected cases, cochlear implantation can be successful after a translabyrinthine approach for VS removal and for restoring hearing after failed retrosigmoid hearing preservation surgery. All patients found the cochlear implant offered useful hearing even in the presence of contralateral hearing.

Objective: Hearing loss resulting from bilateral vestibular schwannomas (VSs) has a significant effect on the quality of life of patients with neurofibromatosis Type 2 (NF2). A national consensus protocol was produced in England as a guide for cochlear implantation (CI) and auditory brainstem implantation (ABI) in these patients., Study Design: Consensus statement., Setting: English NF2 Service., Participants: Clinicians from all 4 lead NF2 units in England., Main Outcome Measures: A protocol for the assessment, insertion and rehabilitation of CI and ABI in NF2 patients., Results: Patients should undergo more detailed hearing assessment once their maximum aided speech discrimination score falls below 50% in the better hearing ear. Bamford-Kowal-Bench sentence testing scores below 50% should trigger assessment for auditory implantation, as recommended by the National Institute for Clinical Excellence guidelines on CI. Where this occurs in patients with bilateral stable VS or a unilateral stable VS where the contralateral cochlear nerve was lost at previous surgery, CI should be considered. Where VS surgery is planned, CI should be considered where cochlear nerve preservation is thought possible, otherwise an ABI should be considered. Intraoperative testing using electrically evoked auditory brainstem responses or cochlear nerve action potentials may be used to determine whether a CI or ABI is inserted., Conclusion: The NF2 centers in England agreed on this protocol. Multisite, prospective assessments of standardized protocols for auditory implantation in NF2 provide an essential model for evaluating candidacy and outcomes in this challenging patient population.

The assessment process is critical in deciding whether a profoundly deaf child with cochlear nerve deficiency (CND) will be suitable for a cochlear or auditory brainstem implant (ABI). Magnetic resonance imaging (MRI) using submillimetric T2 weighted gradient echo or turbo spin echo sequences is mandatory for all profoundly deaf children to diagnose CND. Evidence of audition on behavioural or electrophysiological tests following both auditory and electrical stimulation sometimes allows identification of significant auditory tissue not visible on MRI. In particular electric auditory brainstem response (EABR) testing may allow some quantification of auditory tissue and help decide whether a cochlear implant will be beneficial. Age and cognitive development are the most critical factors in determining ABI benefit. Hearing outcomes from both cochlear implants and ABIs are variable and likely to be limited in children with CND. A proportion of children will get no benefit. Usually the implants would be expected to provide recognition of environmental sounds and understanding of simple phonetics. Most children will not develop normal speech and they will often need to learn to communicate with sign language. The ABI involves a major neurosurgical procedure and at present the long term outcomes are unknown. It is therefore essential that parents who are considering this intervention have plenty of time to consider all aspects and the opportunity for in depth discussion.

Objectives: To analyse the long-term outcome of translabyrinthine surgery for vestibular schwannoma (VS) in neurofibromatosis type 2 (NF2). RESEARCH TYPE: Retrospective cohort study., Setting: Two tertiary referral NF2 units., Patients: One hundred and forty eight translabyrinthine operations for patients with VS were performed. Preoperative stereotactic radiotherapy had been performed on 12(9.4%) patients., Results: Mean tumour size was 3.1 cm. Total tumour excision was achieved in 66% of cases, capsular remnants were left in 24% of cases, and subtotal excision was achieved in 5% and partial removal was achieved in 5%. The radiological residual/recurrence rate was 13.9%. The perioperative mortality was 1.6%. At 2 years postoperatively, facial function was expressed in terms of House-Brackmann score (HB): HB 1 in 53.4%, HB 1/2 in 61.3%, HB 1-3 in 83.2% and HB 4-6 in 16.8%. All nine patients who underwent surgery following failed stereotactic radiotherapy had HB 3 function or better. Among 9.5% of the cases, 14 facial nerves were lost during surgery and repaired using direct anastomosis or grafting. There was no tinnitus present preoperatively in 27% of the cases, and 22% of patients developed tinnitus postoperatively. In patients with preoperative tinnitus, 61% remained the same, 17% got it resolved and only in 21% it worsened. The preoperative hydrocephalus rate was 26%, and among 15% of the cases five ventriculo-peritoneal (VP) shunts were performed. The cerebrospinal fluid leak rate was 2.5%. Fifty-six patients underwent auditory brainstem implantation (ABI) and two patients had cochlear implant (CI) sleepers inserted., Conclusions: The management of patients with NF2 presents the clinician with a formidable challenge with many patients still presenting themselves late with the neurological compromise and a large tumour load. There is still an argument for the management by observation until the neurological compromise dictates interventional treatment particularly with the option of hearing rehabilitation with ABI or CI. The translabyrinthine approach provides a very satisfactory means of reducing the overall tumour volume.

Neurofibromatosis type 2 (NF2) is an autosomal dominant inherited tumor predisposition syndrome caused by mutations in the NF2 gene on chromosome 22. Affected individuals develop schwannomas typically involving both vestibular nerves leading to hearing loss and eventual deafness. Rehabilitation with brainstem implants and in some cases cochlear implants is improving this outcome. Schwannomas also occur on other cranial nerves, on spinal nerve roots and peripheral nerves, and intracutaneously as plaques. Cranial and spinal meningiomas and spinal ependymomas are other common tumors. Fifty to sixty percent of patients represent de novo mutations and as many as 33% of these are mosaic for the underlying disease causing mutation. Truncating mutations (nonsense, frameshift insertions/deletions) are the most frequent germline events and cause the most severe disease, whilst single and multiple exon deletions are common and are usually associated with milder NF2. Neurological deficits are a major feature of the condition and neurologists have a pivotal role in assigning symptoms to lesions and in managing neuropathies. NF2 represents a difficult management problem with most patients facing substantial morbidity and reduced life expectancy. Surgery remains the focus of current management although watchful waiting and occasionally radiation treatment have a role. We are seeing the advent of tailored drug therapies aimed at the genetic level and these are likely to provide huge improvements for this devastating, life-limiting condition., (Copyright © 2013 Elsevier B.V. All rights reserved.)