Cochlear Implantation in Children with Enlarged Vestibular Aqueduct: A Systematic Review of Surgical Implications and Outcomes.

OBJECTIVES: This study investigated age at implantation, improvement in hearing and speech perception outcomes, as well as surgical complications in pediatric cochlear implant recipients with Pendred Syndrome (PS) or non-syndromic enlarged vestibular aqueduct (NSEVA). DESIGN: A systematic review of the literature between 1984 and 2021 was performed. Two independent reviewers performed abstract and full-text screening using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The inclusion criteria were: English language, cochlear implant, age at implantation available, age <18 years, PS, Mondini malformation, and enlarged vestibular aqueduct. Full-text analysis was completed using the National Institute of Health assessment tool for case series and case-control studies. Studies were also graded according to the Oxford Centre for Evidence-Based Medicine grading system. RESULTS: In total, 198 studies were identified and screened, and 55 studies were included for analysis. Audiological outcomes were available in 46 studies, and the four-frequency pure-tone audiogram average improved by 60 to 78 dB HL due to cochlear implantation. Auditory performance and speech intelligibility scores increased by 44%. The overall average implantation age was 60 months. The implantation age was 21 months lower in the studies where individuals were implanted after the year 2000 compared with those implanted before the year 2000. Perilymph gusher/oozing was the most common surgical incident reported, occurring in 187 of 1572 implantations. CONCLUSIONS: In children with PS/NSEVA, cochlear implantation improves pure-tone average by 60 to 78 dB HL and capacity of auditory performance/speech intelligibility by 44%. The implantation age for these children has decreased during the last two decades but is still somewhat higher than reported for unselected pediatric cochlear implantation. Perilymph gusher/oozing is the most common surgical complication.

Tinnitus suppression in a prospective cohort of 45 cochlear implant recipients: occurrence, degree and correlates.

OBJECTIVE: To determine tinnitus prevalence and severity in a cohort of unselected first-time cochlear implant (CI) recipients whose primary motive for CI was sensorineural hearing loss (SNHL), and to evaluate the effect of CI on tinnitus after cochlear implantation. METHODS: Prospective longitudinal study of 45 adult CI recipients with moderate to profound SNHL. Patients completed the Danish version of the Tinnitus Handicap Inventory (THI) and a visual analogue scale (VAS) for tinnitus burden before implantation, 4 months after implantation and 14 months after implantation. RESULTS: The study included 45 patients, of which 29 (64%) had pre-implant tinnitus. Median THI score (IQR) significantly decreased from 20 (34) to 12 (24) at first follow-up (p < 0.05) and to 6 points (17) at second follow-up (p < 0.001). Median VAS (IQR) for tinnitus burden decreased from 33 (62) to 17 (40; p = 0.228) and 12 (27, p < 0.05) at the first and second follow-ups, respectively. Tinnitus was totally suppressed in 19% of patients, improved in 48%, remained unchanged in 19% and worsened in 6%. 2 patients reported new tinnitus. At the second follow-up, 74% of patients had slight or no tinnitus handicap, 16% had mild handicaps, 6% had moderate handicaps, and 3% had severe handicaps. High pre-implant THI and VAS scores correlated with greater decrease in THI scores over time. CONCLUSION: 64% of the patients with SNHL had pre-implant tinnitus, which was decreased 4 and 14 months after implantation. Overall, 68% of patients with tinnitus improved their tinnitus handicap after CI. Patients with higher THI and VAS scores had a larger decline and the highest benefits in terms of tinnitus handicap improvement. The study findings demonstrate that the majority of patients with moderate to profound SNHL eligible for cochlear implantation benefit from complete or partial tinnitus suppression and improved quality of life after implantation.

Intratympanic corticosteroids for sudden sensorineural hearing loss.

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is common, and defined as a sudden decrease in sensorineural hearing sensitivity of unknown aetiology. Systemic corticosteroids are widely used, however their value remains unclear. Intratympanic injections of corticosteroids have become increasingly common in the treatment of ISSNHL. OBJECTIVES: To assess the effects of intratympanic corticosteroids in people with ISSNHL. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2021, Issue 9); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials (search date 23 September 2021). SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving people with ISSNHL and follow-up of over a week. Intratympanic corticosteroids were given as primary or secondary treatment (after failure of systemic therapy). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, including GRADE to assess the certainty of the evidence. Our primary outcome was change in hearing threshold with pure tone audiometry. Secondary outcomes included the proportion of people whose hearing improved, final hearing threshold, speech audiometry, frequency-specific hearing changes and adverse effects. MAIN RESULTS: We included 30 studies, comprising 2133 analysed participants. Some studies had more than two treatment arms and were therefore relevant to several comparisons. Studies investigated intratympanic corticosteroids as either primary (initial) therapy or secondary (rescue) therapy after failure of initial treatment. 1. Intratympanic corticosteroids versus systemic corticosteroids as primary therapy We identified 16 studies (1108 participants). Intratympanic therapy may result in little to no improvement in the change in hearing threshold (mean difference (MD) -5.93 dB better, 95% confidence interval (CI) -7.61 to -4.26; 10 studies; 701 participants; low-certainty). We found little to no difference in the proportion of participants whose hearing was improved (risk ratio (RR) 1.04, 95% CI 0.97 to 1.12; 14 studies; 972 participants; moderate-certainty). Intratympanic therapy may result in little to no difference in the final hearing threshold (MD -3.31 dB, 95% CI -6.16 to -0.47; 7 studies; 516 participants; low-certainty). Intratympanic therapy may increase the number of people who experience vertigo or dizziness (RR 2.53, 95% CI 1.41 to 4.54; 1 study; 250 participants; low-certainty) and probably increases the number of people with ear pain (RR 15.68, 95% CI 6.22 to 39.49; 2 studies; 289 participants; moderate-certainty). It also resulted in persistent tympanic membrane perforation (range 0% to 3.9%; 3 studies; 359 participants; very low-certainty), vertigo/dizziness at the time of injection (1% to 21%, 3 studies; 197 participants; very low-certainty) and ear pain at the time of injection (10.5% to 27.1%; 2 studies; 289 participants; low-certainty). 2. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy We identified 10 studies (788 participants). Combined therapy may have a small effect on the change in hearing threshold (MD -8.55 dB better, 95% CI -12.48 to -4.61; 6 studies; 435 participants; low-certainty). The evidence is very uncertain as to whether combined therapy changes the proportion of participants whose hearing is improved (RR 1.27, 95% CI 1.15 to 1.41; 10 studies; 788 participants; very low-certainty). Combined therapy may result in slightly lower (more favourable) final hearing thresholds but the evidence is very uncertain, and it is not clear whether the change would be important to patients (MD -9.11 dB, 95% CI -16.56 to -1.67; 3 studies; 194 participants; very low-certainty). Some adverse effects only occurred in those who received combined therapy. These included persistent tympanic membrane perforation (range 0% to 5.5%; 5 studies; 474 participants; very low-certainty), vertigo or dizziness at the time of injection (range 0% to 8.1%; 4 studies; 341 participants; very low-certainty) and ear pain at the time of injection (13.5%; 1 study; 73 participants; very low-certainty).  3. Intratympanic corticosteroids versus no treatment or placebo as secondary therapy We identified seven studies (279 participants). Intratympanic therapy may have a small effect on the change in hearing threshold (MD -9.07 dB better, 95% CI -11.47 to -6.66; 7 studies; 280 participants; low-certainty). Intratympanic therapy may result in a much higher proportion of participants whose hearing is improved (RR 5.55, 95% CI 2.89 to 10.68; 6 studies; 232 participants; low-certainty). Intratympanic therapy may result in lower (more favourable) final hearing thresholds (MD -11.09 dB, 95% CI -17.46 to -4.72; 5 studies; 203 participants; low-certainty). Some adverse effects only occurred in those who received intratympanic injection. These included persistent tympanic membrane perforation (range 0% to 4.2%; 5 studies; 185 participants; very low-certainty), vertigo or dizziness at the time of injection (range 6.7% to 33%; 3 studies; 128 participants; very low-certainty) and ear pain at the time of injection (0%; 1 study; 44 participants; very low-certainty).  4. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy We identified one study with 76 participants. Change in hearing threshold was not reported. Combined therapy may result in a higher proportion with hearing improvement, but the evidence is very uncertain (RR 2.24, 95% CI 1.10 to 4.55; very low-certainty). Adverse effects were poorly reported with only data for persistent tympanic membrane perforation (rate 8.1%, very low-certainty). AUTHORS' CONCLUSIONS: Most of the evidence in this review is low- or very low-certainty, therefore it is likely that further studies may change our conclusions.   For primary therapy, intratympanic corticosteroids may have little or no effect compared with systemic corticosteroids. There may be a slight benefit from combined treatment when compared with systemic treatment alone, but the evidence is uncertain. For secondary therapy, there is low-certainty evidence that intratympanic corticosteroids, when compared to no treatment or placebo, may result in a much higher proportion of participants whose hearing is improved, but may only have a small effect on the change in hearing threshold. It is very uncertain whether there is additional benefit from combined treatment over systemic steroids alone. Although adverse effects were poorly reported, the different risk profiles of intratympanic treatment (including tympanic membrane perforation, pain and dizziness/vertigo) and systemic treatment (for example, blood glucose problems) should be considered when selecting appropriate treatment.

Assessing competence in cochlear implant surgery using the newly developed Cochlear Implant Surgery Assessment Tool.

PURPOSE: To develop and gather validity evidence for a novel tool for assessment of cochlear implant (CI) surgery, including virtual reality CI surgery training. METHODS: Prospective study gathering validity evidence according to Messick's framework. Four experts developed the CI Surgery Assessment Tool (CISAT). A total of 35 true novices (medical students), trained novices (residents) and CI surgeons performed two CI-procedures each in the Visible Ear Simulator, which were rated by three blinded experts. Classical test theory and generalizability theory were used for reliability analysis. RESULTS: The CISAT significantly discriminated between the three groups (p < 0.001). The generalizability coefficient was 0.76 and most of the score variance (53.3%) was attributable to the participant and only 6.8% to the raters. When exploring a standard setting for CI surgery, the contrasting groups method suggested a pass/fail score of 36.0 points (out of 55), but since the trained novices performed above this, we propose using the mean CI surgeon performance score (45.3 points). CONCLUSION: Validity evidence for simulation-based assessment of CI performance supports the CISAT. Together with the standard setting, the CISAT might be used to monitor progress in competency-based training of CI surgery and to determine when the trainee can advance to further training.

The impact and prevalence of SARS-CoV-2 in patients with head and neck cancer and acute upper airway infection in a tertiary otorhinolaryngology referral center in Denmark.

PURPOSE: To determine the prevalence of SARS-CoV-2 at a Danish tertiary referral otorhinolaryngology clinic during the first wave of the COVID-19 pandemic among patients with suspected acute upper airway infection (UAI) and patients operated for head and neck cancer (HNC), respectively. To monitor changes in the number of patient encounters for acute UAI and the number of referrals for the workup of HNC. TRIAL REGISTRATION: NCT-04356560 (Clinicaltrials.gov). METHODS: Prospective enrolled case series of all patients with suspected acute UAI (n = 88) and of patients undergoing surgery for HNC (n = 96), respectively, from March 23rd to May 5th, 2020, at a public tertiary referral otorhinolaryngology clinic in Denmark. SARS-CoV-2 was diagnosed with nasopharyngeal and oropharyngeal swabbing. Patients with suspected acute UAI had symptoms and definitive diagnoses registered in a database. Trends in the number of referrals and patient encounters were retrieved from an electronic patient journal system and analyzed retrospectively. RESULTS: Eighty-eight patients with acute UAI were enrolled including 55 men and 34 women, median age of 31 years (range: 10 months to 82 years). One patient (1.1%) tested positive. Among 96 patients operated for HNC, zero tested positive. The number of referrals for HNC workup, and patient encounters for peritonsillar abscesses, decreased markedly in the first 3 weeks. CONCLUSION: The prevalence of SARS-CoV-2 during the first 6 weeks of the first wave was minimal among patients with acute UAI and zero among patients operated for HNC. The decrease in referrals for the workup of HNC may increase time to treatment initiation and patient morbidity.

COVID-19 infection rate among tertiary referral center otorhinolaryngology healthcare workers.

IMPORTANCE: Otorhinolaryngology is considered one of the medical specialties with a high risk for exposure to corona disease 2019 (COVID-19). Uncontrolled transmission in a hospital department poses a risk to both healthcare workers (HCWs) and patients. OBJECTIVE: To monitor SARS-CoV-2 incidence, transmission, and antibody development among HCWs to identify high risk procedures, pathways, and work areas within the department. METHODS: Prospective cohort study of HCWs using repetitive oro- and nasopharygeal swab samples, antibody tests, and self-reported symptoms questionnaires at a tertiary referral center in Copenhagen, Denmark. RESULTS: 347/361 (96%) HCWs participated. Seven (1.9%) were positive on swab tests and none had symptoms. Fifteen (4.2%) developed antibodies. Only one case of potential transmission between HCWs was identified. Infection rates were low and no procedures or areas within the department were identified as exposing HCWs to a higher risk. CONCLUSIONS AND RELEVANCE: Adherence to the surveillance program was high. The low incidence among HCW during the first wave of the COVID-19 pandemic may reflect local transmission and infection control precautions, as well as a low infectious burden in the Danish society.

Appropriateness for SARS-CoV-2 vaccination for otolaryngologist and head and neck surgeons in case of pregnancy, breastfeeding, or childbearing potential: Yo-IFOS and CEORL-HNS joint clinical consensus statement.

PURPOSE: SARS-CoV-2 vaccines are a key step in fighting the pandemic. Nevertheless, their rapid development did not allow for testing among specific population subgroups such as pregnant and breastfeeding women, or elaborating specific guidelines for healthcare personnel working in high infection risk specialties, such as otolaryngology (ORL). This clinical consensus statement (CCS) aims to offer guidance for SARS-CoV-2 vaccination to this high-risk population based on the best evidence available. METHODS: A multidisciplinary international panel of 33 specialists judged statements through a two-round modified Delphi method survey. Statements were designed to encompass the following topics: risk of SARS-Cov-2 infection and use of protective equipment in ORL; SARS-Cov-2 infection and vaccines and respective risks for the mother/child dyad; and counseling for SARS-CoV-2 vaccination in pregnant, breastfeeding, or fertile healthcare workers (PBFHW). All ORL PBFHW were considered as the target audience. RESULTS: Of the 13 statements, 7 reached consensus or strong consensus, 2 reached no consensus, and 2 reached near-consensus. According to the statements with strong consensus otorhinolaryngologists-head and neck surgeons who are pregnant, breastfeeding, or with childbearing potential should have the opportunity to receive SARS-Cov-2 vaccination. Moreover, personal protective equipment (PPE) should still be used even after the vaccination. CONCLUSION: Until prospective evaluations on these topics are available, ORL-HNS must be considered a high infection risk specialty. While the use of PPE remains pivotal, ORL PBFHW should be allowed access to SARS-CoV-2 vaccination provided they receive up-to-date information.

Tumor miRNA expression profile is related to vestibular schwannoma growth rate.

OBJECTIVE: Our objective was to investigate if the tumor microRNA (miRNA) expression profile was related to tumor growth rate. Growth-related miRNAs might be potential targets for future therapeutic intervention. MATERIAL AND METHODS: Tumor tissue was sampled during surgery of patients with a sporadic vestibular schwannoma. Tumor growth rate was determined by tumor measurement on the two latest pre-operative MRI scans. Tumor miRNA expression was analyzed using the Affymetrix Gene Chip® protocol, and CEL files were generated using GeneChip® Command Console® Software and normalized using Partek Genomics Suite 6.5. The CEL files were analyzed using the statistical software program R. Principal component analysis, affected gene ontology analysis, and analysis of miRNA expression fold changes were used for analysis of potential relations between miRNA expression profile and tumor growth rate. RESULTS AND CONCLUSION: Tumor miRNA expression is related to the growth rate of sporadic vestibular schwannomas. Rapid tumor growth is associated with deregulation of several miRNAs, including upregulation of miR-29abc, miR-19, miR-340-5p, miR-21, and miR-221 and downregulation of miR-744 and let-7b. Gene ontologies affected by the deregulated miRNAs included neuron development and differentiation, gene silencing, and negative regulation of various biological processes, including cellular and intracellular signaling and metabolism.

Sporadic and NF2-associated vestibular schwannoma surgery and simultaneous cochlear implantation: a comparative systematic review.

PURPOSE: Cochlear implantation (CI) in patients with sensorineural hearing loss caused by a vestibular schwannoma (VS) represents a unique subtype of hearing rehabilitation, as the outcome may be compromised by vestibulocochlear nerve injury as part of the natural VS history or due to iatrogenic trauma induced by surgical tumor removal. This paper aims to review and report contemporary knowledge and practice regarding feasibility and outcomes of simultaneous vestibular schwannoma resection and cochlear implantation to serve as a reference and guide for future surgery and studies. METHODS: The current literature was searched systematically according to the PRISMA guidelines and after criteria-based selection, 29 studies were identified, including a total of 86 patients who had undergone surgical resection of a vestibular schwannoma and subsequent cochlear implantation in a single procedure. RESULTS: The postoperative outcomes were reported with a high degree of heterogeneity, hindering a proper meta-analysis. However, pooling those cases with reported speech discrimination outcomes demonstrated mean scores equivalent to moderate-to-high performance. A few cases had no audibility. A positive cochlear nerve test result was not a secure positive predictor of success. Complications were rare. CONCLUSION: NF2-associated and sporadic VS had good and comparable postoperative outcomes despite significant differences in tumor size, location and surgical approach.

Developing a national e-learning course in otorhinolaryngology: the Danish experience.

PURPOSE: E-learning provides a flexible and effective approach to learning and is increasingly used in otorhinolaryngology (ORL). We developed a national theoretical e-learning course for ORL trainees and describe our experiences with implementation as well as piloting the e-learning course. METHODS: E-learning course content was developed as structured multiple choice quizzes for the European core curriculum textbook. An open-source learning management system was adapted for a self-paced e-learning course. We piloted the e-learning course as a non-mandatory option for the 15 residents participating in the Danish 4-day national training course in rhinology in February 2019. A post-course survey was sent out to the participants and used in the evaluation along with activity data from the learning management system. RESULTS: Fourteen out of 15 trainees participated in the e-learning course. Nine participants completed > 95% of the course. The activity data demonstrated that participants with the highest completion rate typically began well in advance of the course (> 2 months). Overall the e-learning course was rated positively in relation to learning and as preparation for the national training course. Participants responded that the level of the e-learning course was higher than and also at times in slight incongruity with the content of the national curriculum. Participants would like protected study time for e-learning activities in their residency program. All participants responded that they would use e-learning in relation to future national training courses. CONCLUSIONS: Developing a national e-learning course is feasible and is well-received by trainees as well as other educational stakeholders.

Facial nerve schwannomas presenting with vestibular dysfunction: a case series.

Facial nerve schwannomas (FS) can symptomatically mimic vestibular schwannomas (VS). In addition, FS can be difficult to distinguish from VS on magnetic resonance imaging (MRI). Although disequilibrium is not uncommon in patients with FS, no previous studies have investigated the vestibular function in such patients. Three cases of FS presented vestibular dysfunction as measured with caloric test, video head impulse test (VHIT), and vestibular evoked myogenic potentials (VEMPs). All patients in this study had a considerable affection of the vestibular function as assessed by the vestibular test panel. Audiovestibular evaluation of FS provides important information that may influence treatment strategy. As VS, FS should be evaluated with vestibular tests prior to intervention.

Innate immune defense in the inner ear - mucines are expressed by the human endolymphatic sac.

The human endolymphatic sac has been shown recently to have immunological capacities and has thus been proposed as the main entity protecting the inner ear from pathogen invasion, equivalent to mucosa-associated lymphoid tissue (MALT). Although the sac expresses molecules of the innate immune system, the potential expression of members of the important mucin family has not been detailed. Thus, this paper explores endolymphatic sac expression of a number of mucins and mucin precursors. Twelve fresh tissue samples from the human endolymphatic sac were obtained during translabyrinthine surgery. The expression of Mucin 1, 2, 5B/AC and 16, as well as the core structure elements (mucin precursors) T-antigen, Tn-antigen and Sialyl-Tn-antigen was investigated by immunohistochemistry. The endolymphatic sac epithelium expressed MUC1 (both apically towards the endolymphatic sac (ES) lumen and basally towards the capillary network), MUC 16 and Tn-antigen. There was no labeling after incubation with antibodies against T-antigen, sialyl-Tn-antigen, MUC2 and MUC5B/AC. We conclude that the human endolymphatic sac epithelium expresses a number of mucin molecules, which supports the hypothesis of the sac as the primary immunological tissue structure of the inner ear, equivalent to MALT in other organs. The mucins may also play a role in the formation and continuous homeostasis of the inner ear fluids, as well as the pathogenesis of Meniere's disease.

Gene expression, signal transduction pathways and functional networks associated with growth of sporadic vestibular schwannomas.

The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate. Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS. Double stranded cDNA was synthesized from the mRNA and used as template for in vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software. Differential gene expression was defined as a 1.5-fold difference between fast and slow growing tumors (><0.5 ccm/year), employing a p-value <0.01. Deregulated transcripts were matched against established gene ontology. Ingenuity Pathway Analysis was used for identification of signal transduction pathways and functional molecular networks associated with tumor growth. In total 109 genes were deregulated in relation to tumor growth rate. Genes associated with apoptosis, growth and cell proliferation were deregulated. Gene ontology included regulation of the cell cycle, cell differentiation and proliferation, among other functions. Fourteen pathways were associated with tumor growth. Five functional molecular networks were generated. This first study on global gene expression in relation to vestibular schwannoma growth rate identified several genes, signal transduction pathways and functional networks associated with tumor progression. Specific genes involved in apoptosis, cell growth and proliferation were deregulated in fast growing tumors. Fourteen pathways were associated with tumor growth. Generated functional networks underlined the importance of the PI3K family, among others.

Residential traffic noise exposure and vestibular schwannoma - a Danish case-control study.

BACKGROUND: Few risk factors for sporadic vestibular schwannoma (VS) are known. Several studies have proposed an increased risk with occupational noise exposure, whereas no studies have investigated residential traffic noise exposure as a risk factor. The present study investigated if residential traffic noise was associated with vestibular schwannoma in a large, population-based Danish case-control study. MATERIAL AND METHODS: We identified 1454 VS cases, age above 30 years at diagnosis, between 1990 and 2007. For each case, we selected two random population controls, matched on sex and year of birth. Road and railway traffic noise at the residence was calculated for all present and historical addresses between 1987 and index date. Associations between traffic noise and risk for VS were estimated using conditional logistic regression, adjusted for education, disposable personal income, cohabitation status, railway noise exposure, municipal population density, and municipal income. RESULTS: A two-year time-weighted mean road traffic noise exposure was associated with an adjusted odds ratio of 0.92 (0.82-1.03) for developing VS, per 10 dB increment. There was no clear trend in categorical analyses. Similarly, linear and categorical analyses of residential railway noise did not suggest an association. We found no interaction with demographics, year of diagnosis, individual and municipal socioeconomic variables, and railway noise exposure. The results did not differ by tumor side, spread or size. CONCLUSIONS: The present study does not suggest an association between residential traffic noise and VS.

The middle ear immune defense changes with age.

Otitis media is a common disease in childhood. In adults, the disease is relatively rare, but more frequently associated with complications. Possible reasons for this discrepancy are age-related differences in pathogen exposure, anatomy of the Eustachian tube and immune system. The objective of this study was to analyze the relationship between age and the mucosal immune system in the middle ear. It is hypothesized that genes involved in the middle ear immune system will change with age. A comprehensive assessment of these genetic differences using the techniques of complementary DNA has not been performed. Complementary DNA microarray technology was used to identify immune-related genes differentially expressed between the normal middle ear mucosa of young (10 days old) and adult rats (80 days old). Data were analyzed using tools of bioinformatics. A total of 260 age-related genes were identified, of which 51 genes were involved in the middle ear mucosal immune system. Genes related to the innate immune system, including alpha-defensin, calcium-binding proteins S100A9 and S100A8, were upregulated in young rats, whereas genes related to the adaptive immune system, including CD3 molecules, zeta-chain T-cell receptor-associated protein kinase and linker of activated T-cells, were upregulated in the adult. This study concludes that the normal middle ear immune system changes with age. Genes related to the innate immune system are upregulated in young rats, whereas genes related to the adaptive immune system are upregulated in adults.

Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 - a retrospective case series.

PURPOSE: The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS). Approximately 80% of NF2 patients also have intracranial meningiomas. Vascular endothelial growth factor (VEGF) is expressed in both NF2-related and sporadic occurring meningiomas and anti-VEGF therapy (bevacizumab) may, therefore, be beneficial in NF2-related meningiomas. The purpose of the study was to report the effect of bevacizumab on meningiomas in NF2 patients. MATERIALS AND METHODS: We retrospectively reviewed the effect of bevacizumab on the cross-sectional area (CSA) of 14 intracranial meningiomas in 7 NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every two weeks for six months and 15 mg/kg every three weeks thereafter. Patients were evaluated according to the modified Macdonald criteria with repeated magnetic resonance (MR) scans. RESULTS: The median duration of therapy was 27 months (range 16-34) and 42 MR scans (median 8, range 4-11) were reviewed. The median annual change in meningioma CSA prior to bevacizumab was 2% (range -4%-+76%). During treatment, a decrease in meningioma CSA was observed in 5 of 14 meningiomas (36%) in 5 of 7 patients (71%). The median decrease in CSA was -10% (range -3%--25%). One meningioma (7%) progressed and the remaining (93%) had stable disease. CONCLUSIONS: Bevacizumab may slow or reverse the growth of some NF-related meningiomas. However, we have previously reported a fatal case of intracerebral hemorrhage following bevacizumab in NF2 patients, wherefore, this effect needs to be balanced carefully against the risk of side effects.

Endolymphatic sac involvement in bacterial meningitis.

The commonest sequelae of bacterial meningitis are related to the inner ear. Little is known about the inner ear immune defense. Evidence suggests that the endolymphatic sac provides some protection against infection. A potential involvement of the endolymphatic sac in bacterial meningitis is largely unaccounted for, and thus the object of the present study. A well-established adult rat model of Streptococcus pneumoniae meningitis was employed. Thirty adult rats were inoculated intrathecally with Streptococcus pneumoniae and received no additional treatment. Six rats were sham-inoculated. The rats were killed when reaching terminal illness or on day 7, followed by light microscopy preparation and PAS-Alcian blue staining. The endolymphatic sac was examined for bacterial invasion and leukocyte infiltration. Neither bacteria nor leukocytes infiltrated the endolymphatic sac during the first days. Bacteria invaded the inner ear through the cochlear aquaduct. On days 5-6, the bacteria invaded the endolymphatic sac through the endolymphatic duct subsequent to invasion of the vestibular endolymphatic compartment. No evidence of direct bacterial invasion of the sac through the meninges was found. Leukocyte infiltration of the sac occurred prior to bacterial invasion. During meningitis, bacteria do not invade the endolymphatic sac through the dura, but solely through the endolymphatic duct, following the invasion of the vestibular system. Leukocyte infiltration of the sac occurs prior to, as well as concurrent with bacterial invasion. The findings support the endolymphatic sac as part of an innate immune defense system protecting the inner ear from infection.

The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2.

The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS) and severe hearing loss is common in NF2 patients. Vascular endothelial growth factor (VEGF) expression level in NF2 correlates with tumour growth rate and bevacizumab, a VEGF-binding antibody, has previously been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg/kg was administered every third week. Patients were evaluated with repeated audiometries, MR scans and clinical evaluations. Radiological response was defined as a 20 % or greater reduction in VS volume. A total of 398 treatments (median 36) were administered and the median duration on therapy was 22 months (range 7-34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported subjective benefit in neurological symptoms, including improved hearing. Toxicity was in general manageable; however, one patient died from cerebral haemorrhage which was possibly related to therapy. In conclusion, bevacizumab improved hearing and reduced the size of VS in some patients with progressive NF2 which corroborates previous findings; however, the risk of severe side effects should be carefully considered and discussed with the patients prior to treatment.

Stereotactic radiotherapy for vestibular schwannoma.

BACKGROUND: Vestibular schwannomas (acoustic neuromas) are common benign tumours that arise from the Schwann cells of the vestibular nerve. Management options include observation with neuroradiological follow-up, microsurgical resection and stereotactic radiotherapy. OBJECTIVES: To assess the effect of stereotactic radiotherapy compared to observation, microsurgical resection, any other treatment modality, or a combination of two or more of the above approaches for vestibular schwannoma. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials; PubMed; EMBASE; CINAHL; Web of Science; CAB Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the search was 24 July 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs) exploring the efficacy of stereotactic radiotherapy compared with observation alone, microsurgical resection or any other possible treatment or combination of treatments in patients with a cerebellopontine angle tumour up to 3 cm in diameter, presumed to be a vestibular schwannoma. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: No studies met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: There is no high quality evidence in the literature from RCTs to determine whether stereotactic radiotherapy is better than microsurgical resection or observation alone for patients with a vestibular schwannoma. In the absence of such evidence, the treatment method should be chosen on an individual basis, taking into consideration the patient's preferences, clinician experience and the availability of radiotherapeutic equipment. With the growing availability of radiotherapeutic equipment, randomised controlled trials should be undertaken to evaluate the role of stereotactic radiotherapy in comparison with other treatment options.

Does Location of Intralabyrinthine Vestibular Schwannoma Determine Objective and Subjective Vestibular Function?

BACKGROUND AND OBJECTIVE: The incidence of intralabyrinthine schwannomas is increasing, and a growing attention is given to the detrimental effects on hearing function. On the contrary, the vestibular profile of intralabyrinthine vestibular schwannomas (VSs) is still not well understood. We aimed to investigate and report the observed relationships between the intralabyrinthine location of the schwannomas and objective and subjective vestibular profile of the patients. METHODS: Retrospective cohort study of 20 consecutive individuals with sporadic intralabyrinthine schwannomas and grouped according to the intralabyrinthine location of the schwannomas. Vestibular testing consisted of the video head impulse test of all three semicircular canals, the caloric test, cervical and ocular vestibular evoked myogenic potentials, and the dizziness handicap inventory. A nonparametric unpaired t test was performed to compare groups, and Fisher's exact test was used for categorical data. RESULTS: The median video head impulse test gains (lateral, anterior, posterior) were 0.40, 0.50, and 0.75 for intravestibular schwannomas and 0.93, 1.52, and 0.91 for intracochlear schwannomas ( p = 0.0001, p = 0.009, p = 0.33), respectively. Caloric unilateral weakness had a median of 100% for intravestibular schwannomas and 14% for intracochlear schwannomas ( p = 0.0001). The mean dizziness handicap inventory was 21 for intravestibular schwannomas and 1 for cochlear schwannomas ( p = 0.02). There were no significant differences in vestibular evoked myogenic potentials according to intralabyrinthine location. CONCLUSION: By both objective and subjective measures, intralabyrinthine schwannomas with an intravestibular component has significantly worse vestibular function than schwannomas with purely cochlear involvement.