Is Early Progression to Bilateral Involvement in Menière's Disease a Poor Prognostic Indicator? Objective: To investigate differences in the clinical features of bilateral Menière's disease (BMD) with early and late bilateral involvement. Study Design: A retrospective case-comparison study. Setting: Tertiary referral center. Patients: In total, 25 patients with definite BMD were enrolled. Patients with bilateral involvement with a transition interval shorter than 1 month were considered to have synchronous BMD, whereas the others had metachronous BMD. Interventions: We investigated differences in prognosis as defined by changes in the number of vertigo attacks after treatment, demographics, comorbidities, and inner ear function according to the transition interval from unilateral to bilateral involvement. Main Outcome Measure: We investigated other appropriate cut-off values in the interval from first- to second-ear involvement to predict poor prognosis. Results: Receiver operating characteristic curve analysis revealed that a cut-off value of < 18-month interval exhibited maximum sensitivity and specificity for predicting poor prognosis. According to this value, we categorized patients into the early bilateral involvement group (EBIG, < 18 months’ interval) and the late bilateral involvement group (LBIG, ≥ 18 months’ interval). Patients with synchronous BMD and patients in the EBIG group exhibited poorer prognosis compared with patients with metachronous BMD and those in LBIG (p = 0.011 and p ≤ 0.001). Demographics, hearing threshold, vestibular deficit, and comorbidities were not significantly different between the two groups (p > 0.05). None of the patients exhibited systemic autoimmune disease. Conclusion: BMD with early bilateral progression exhibited poorer prognosis compared with late bilateral progression. Address correspondence and reprint requests to Sung Huhn Kim, M.D., Ph.D., Department of Otorhinolaryngology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; E-mail: fledermaus@yuhs.ac This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (2017R1A2B4008850) to S.H.K. The authors disclose no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://journals.lww.com/otology-neurotology). Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Characterizing Insertion Pressure Profiles During Cochlear Implantation: Simultaneous Fluoroscopy and Intracochlear Pressure Measurements Background: Combined electrical-acoustical stimulation (EAS) has gained popularity as patients with residual hearing are increasingly undergoing cochlear implantation. Preservation of residual hearing correlates with hearing outcomes, but loss of hearing occurs in a subset of these patients. Several mechanisms have been proposed as causing this hearing loss; we have previously described high amplitude pressure transients, equivalent to high-level noise exposures, in the inner ear during electrode insertion. The source of these transients has not been identified. Methods: Cadaveric human heads were prepared with an extended facial recess. Fiber-optic pressure sensors were inserted into the scala vestibuli and scala tympani to measure intracochlear pressures. Two cochlear implant (CI) electrode styles (straight and perimodiolar) were inserted during time-synced intracochlear pressures and video fluoroscopy measurements. Results: CI electrode insertions produced pressure transients in the cochlea up to 160 to 170 dB pSPL equivalent for both styles, consistent with previous results. However, the position of the electrode within the cochlea when transients were generated differed (particularly contact with the medial or lateral walls). Conclusions: These results begin to elucidate the insertion pressure profiles of CI electrodes, which can be used to improve CI electrode designs and facilitate “silent-insertions” to improve chances of hearing preservation. Address correspondence and reprint requests to Nathaniel T. Greene, Ph.D., Department of Otolaryngology, University of Colorado School of Medicine, 12631 E. 17th Ave., B205, Aurora, CO 80045; E-mail: Nathaniel.Greene@CUAnschutz.EDU Author contribution statement: J.R.G., J.P., S.P.C., and N.T.G. designed and performed the experiments; J.R.G., N.D.C., R.M.B.H., J.P., S.P.C., and N.T.G. reviewed data and provided interpretive analysis; J.R.G., N.D.C., R.M.B.H., S.P.C., and N.T.G. analyzed data and wrote the paper. All authors discussed the results and implications and commented on the manuscript at all stages. Funding: None to report. S.P.C. is a consultant for Cochlear Corporation. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

The Conditional Probability of Vestibular Schwannoma Growth at Different Time Points after Initial Stability on an Observational Protocol Objective: The natural history of vestibular schwannomas (VS) is well documented in the literature, with tumour growth being paramount to decision making for both surveillance and treatment of these patients. Most previous studies refer to the risk of VS growth over a given period of time; however, this is not useful for counselling patients at different stages of their follow-up, as the risk of tumour growth is likely to be less following each subsequent year that a tumour does not grow. Accordingly, we investigated the conditional probability of VS growth at particular time-points, given a patient has not grown thus far. This Bayesian method of risk stratification allows for more tailored and accurate approximations of the risk of growth versus nongrowth of VS. Methods: Retrospective analysis of a prospectively collected database in a tertiary referral skull base unit, containing all patients diagnosed between 2005 and 2014 with sporadic unilateral VS and a minimum of 5-year surveillance. Results: A total of 341 patients met the inclusion criteria. The mean age at diagnosis was 67 years, the sizes of the VS at diagnosis were intracanalicular in 49%, small in 39%, medium in 11%, and large in 1%. Over the entire 5-year surveillance period, a total of 139 tumours were seen to grow (41%) and 202 did not grow (59%). At 1 year, the probability of growth given that the tumour had not grown to date was seen to be 21%, at 2 years 12%, at 3 years 9%, at 4 years 3%, and at 5 years 2%. The conditional probability of growth of extracanalicular VS was significantly higher in the first year when compared with intracanalicular VS (29% versus 13%, p = 0.01), but there was no such difference in years 2, 3, 4 or 5 (p = 0.60, 0.69, 0.36, 0.39, respectively). Conclusion: This is the first study in the literature concerned specifically with the conditional probability of VS growth. The data presented here can be used to better inform VS patients of their risk of growth at particular time points in their disease—the longer VS have been observed to be stable, the lower the risk of subsequent growth in a given year. Further, an extracanalicular vestibular schwannoma is more likely to grow in the first year compared with an intracanalicular vestibular schwannoma. Our data also adds support to surveillance protocols with increasingly infrequent MRI scans, as after 4 years of not growing, the risk of growth in year 5 falls to <2%. Address correspondence and reprint requests to Manohar Bance, M.D., Department of Skull Base Surgery, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge CB2 0QQ, UK; E-mail: mlb59@cam.ac.uk The authors report no conflicts of interest Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Surgically-Relevant Anatomy of the External Auditory Canal Bulge and Scutum Hypothesis: Anatomic study of the external auditory canal's (EAC) anterior bulge, scutum, and ossicular chain will generate knowledge applicable to safe ear surgery and instrument design. Background: The EAC contains two structures that obscure view of the middle ear: the anterior bulge and the scutum. The dimensions of these structures and their relationships to the ossicular chain have not been previously described. Methods: Cadaveric temporal bones underwent computed tomography scanning, and three-dimensional reconstructions were created. Dimensions and angles of the EAC, its anterior bulge and scutum were measured. Distances to ossicular landmarks and the facial nerve were examined. Results: The anterior EAC had a swan-neck shape. The thinnest portion was located medially and correlated with the canal thickness at the anterior bulge. However the thickness of the anterior bulge was not correlated with its angulation. The scutum averaged 3.8 mm long with a base thickness of 2.3 mm and a mean tip angle of 33 degrees. The short process of the incus was significantly closer to the scutum than other ossicular landmarks. Conclusion: Prominent anterior canal bulges are formed by posterior temporomandibular joints, not thicker bone. The scutum has asymmetric distances to various portions of the ossicles with the incus short process sometimes as close as 0.2 mm, placing it at risk of injury. Address correspondence and reprint requests to Arnaldo L. Rivera, M.D., Department of Otolaryngology—MA 314, One Hospital Drive, Columbia, MO 65212; E-mail: riveraal@health.missouri.edu The scutum portion of this paper was presented at the American Academy of Otolaryngology Head and Neck Surgery Annual Meeting 2018. The authors have no competing interests to disclose. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Is Asymmetric Hearing Loss a Risk Factor for Vestibular Dysfunction? Lesson From Big Data Analysis Based on the Korean National Health and Nutrition Survey Objective: The purpose of this study was to investigate whether asymmetric hearing loss affects vestibular function. Study Design: Retrospective cross-sectional study. Patients: Data from the 2010 Korean National Health and Nutrition Survey for adults aged 40 years or more were used. Interventions: The modified Romberg test and pure-tone audiometry were performed. Data were analyzed using a complex sample χ2 test of independence and complex sample logistic regression analysis. Main Outcome Measures: Vestibular dysfunction and hearing thresholds. Results: The overall prevalence of vestibular dysfunction was 3.3% (95% confidence interval [CI], 2.5–4.3%). In adults more than 40 years of age, multivariate linear regression analyses showed that the odds ratio (OR) of vestibular dysfunction was 3.067 times higher than the reference for a 30-dB difference in hearing thresholds between both ears (CI, 1.481–6.351; p = 0.007) after adjusting for factors associated with vestibular dysfunction. Among these individuals, the risk of equilibrium disturbance was higher in the presence of low-frequency asymmetric hearing loss (OR, 2.148; CI, 1.216–3.793; p = 0.009); on the other hand, high-frequency asymmetry did not lead to a higher risk. Conclusions: As low-frequency asymmetric hearing thresholds tend to coexist with vestibular dysfunction in adults, those with asymmetric hearing loss should be closely monitored. Address correspondence and reprint requests to Sung Huhn Kim, M.D., Ph.D., Department of Otorhinolaryngology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea; E-mail: fledermaus@yuhs.ac This work was supported by a research grant from Jeju National University Hospital in 2018. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Commercial Quinolone Ear Drops Cause Perforations in Intact Rat Tympanic Membranes Hypothesis: Commercial quinolone ear drops may promote the development of perforations (TMPs) in intact tympanic membrane (TMs). Background: Quinolone ear drops have been associated with TMPs after myringotomy +/- tube placement in a drug-specific manner and potentiation by steroids. Methods: Rats were randomized to six groups (10/group), with one ear receiving otic instillation of dexamethasone, ofloxacin, ciprofloxacin, ofloxacin + dexamethasone, ciprofloxacin + dexamethasone, or neomycin + polymyxin + hydrocortisone—all commercial formulations and at standard clinical concentrations—and the contralateral ear receiving saline, twice daily for 10 days. TMs were assessed over 42 days. Results: No TMPs were seen in ears treated with saline, dexamethasone, or neomycin. At day 10, TMPs were seen in one of 10 ofloxacin- and three of 10 ciprofloxacin + dexamethasone-treated ears (p = 0.038). At day 14, the ofloxacin TMP healed. In contrast, the three ciprofloxacin + dexamethasone TMPs remained and one new TMP developed in this group. A ciprofloxacin and an ofloxacin + dexamethasone-treated ears also had TMPs (p = 0.023). By day 21, the ofloxacin + dexamethasone TMP and two of four of the ciprofloxacin + dexamethasone TMPs healed but two new TMPs were seen in ciprofloxacin + dexamethasone ears (p = 0.0006). At day 28, 1 of 10 ciprofloxacin and 4 of 10 ciprofloxacin + dexamethasone-treated ears had TMPs (p = 0.0006). By day 35, only one ciprofloxacin + dexamethasone had TMP (p = 0.42). All TMPS were healed at day 42. Conclusions: Application of commercial quinolone ear drops can cause TMPs in intact TMs. This effect appears to be drug-specific and potentiated by steroids. Address correspondence and reprint requests to Carolyn O. Dirain, Ph.D., Department of Otolaryngology, University of Florida, Box 100264, 1345 Center Drive MSB M2-228, Gainesville, FL 32610-0264; E-mail: ojanoc@ent.ufl.edu None of these commercial entities was involved in the design and conduct of the study or in the interpretation of the data and preparation of the manuscript. Financial support for this study was provided solely by the University of Florida. Dr. Antonelli discloses research support from Alcon Laboratories, Edison Pharmaceuticals, Otonomy, Next Science, and Medtronic ENT; service on Otonomy and Metarmor advisory boards; and speaker sponsorship by Alkem Laboratories and Vindico Medical Education. Dr. Dirain discloses research support from Next Science and Medtronic ENT. Mr. Karnani has no relevant conflicts to disclose. Supplemental digital content is available in the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://journals.lww.com/otology-neurotology). Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Cochlear MRI Signal Change Following Vestibular Schwannoma Resection Depends on Surgical Approach Objective: Information on cochlear MRI signal change following vestibular schwannoma (VS) surgery by the retrolabyrinthine approach (RLA) is nonexisting, and information using the translabyrinthine approach (TLA) is scarce. We aimed to evaluate cochlear MRI fluid signal in patients with a unilateral VS, before and after surgery by the RLA or the TLA, that can have clinical importance for subsequent cochlear implantation feasibility. Study Design: Retrospective cohort study. Setting: University hospital. Patients: One hundred one patients with a unilateral VS. Intervention: VS resection by the TLA or the RLA. Pre- and postoperative T2-weighted MRI. Main Outcome Measure: Cochlear signal change using a semiquantitative system for grading cochlear asymmetry, with grades ranging from 1 (normal fluid signal both sides) to 4 (no fluid signal one side). Results: Seventy-four patients were operated by the TLA and 27 by the RLA. The number of cochleas with grade 3 and 4 asymmetries postoperative was significantly higher than preoperative. The postoperative proportions of grade 1 (TLA 20%, RLA 56%) and grade 2–4 asymmetry (TLA 80%, RLA 44%) were significantly different between the two groups. In the TLA group, 46 patients (62%) demonstrated an increased asymmetry postoperatively, as compared with three patients (11%) in the RLA group. Conclusions: Postoperative decrease of cochlear MRI fluid signal is more likely to occur after translabyrinthine surgery (occurring in 62%), as compared with retrolabyrinthine surgery (occurring in 11%). The decrease of cochlear signal may be due to compromised vascularity or fibrosis. Address correspondence and reprint requests to Niels West, M.D., Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail: westniels@gmail.com Parts of the data were presented at the EAONO conference, June 2018, Copenhagen. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Open Mastoid Cavity Obliteration With a High-Porosity Hydroxyapatite Ceramic Leads to High Rate of Revision Surgery and Insufficient Cavity Obliteration Objective: To assess long-term results and present experience with a high-porosity hydroxyapatite ceramic for obliterating large open mastoid cavities. Study-Design: Cross-sectional cohort study. Setting: Tertiary academic referral center. Patients: All patients who underwent tympanomastoid surgery for chronic middle ear disease or revision surgery with reduction of an open mastoid cavity using a highly porous hydroxyapatite matrix material (HMM) between May 2005 and June 2013 were assessed for eligibility. Twenty three patients (56.9 ± 18.3 yr) were included. Intervention: Primary middle ear surgery or revision surgery using a HMM. Main Outcome Measures: Pure-tone average, computed tomography (CT), and magnetic resonance imaging (MRI) to investigate osseoinduction, osseointegration and presence of cholesteatoma, current quality of life assessed by Zurich Chronic Middle Ear Inventory and change in quality of life post-intervention assessed by the Glasgow Benefit Inventory. Results: Patients were reexamined after a mean follow-up period of 88.3 months (SD 21.4 mo) after obliteration of the open mastoid cavity with HMM. Compared with visit 1, patients showed a significantly reduced ABG at visit 2 (29.22 dB ± 2.71 dB versus 12.77 dB ± 3.46 dB). CT scan was carried out in 21 patients (91%) patients and 17 patients (74%) underwent MRI. Revision surgery was required in a total of 17 cases (74%). In four patients recurrent cholesteatoma was found at follow up. Conclusions: Poor cavity obliteration, a high rate of revision surgery and difficult differentiation between recurrent cholesteatoma and granulation tissue in CT scan was observed. Address correspondence and reprint requests to Nora M. Weiss, Department of Oto-Rhino-Laryngology, Head and Neck Surgery “Otto Körner”, Rostock University Medical Center, Doberaner Strasse 137-139, D-18057 Rostock, Germany; E-mail: nora-magdalena.weiss@med.uni-rostock.de The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Musical Ear Syndrome and Cochlear Explantation: Case Report and Proposal for a Theoretical Framework Objective: To report an unusual case of musical ear syndrome, and to present a theoretical framework for this condition, merging information from the presented case and from former case reports. Patient: A 67-year-old semi-professional musician, who underwent bilateral cochlear implantation and experienced musical ear syndrome, i.e., hearing music, where none was present. Interventions: Cochlear implantation with a bilateral cochlear implant, and cochlear explantation 17 months later. Main Outcome Measure: Report of presence or absence of musical ear syndrome by the patient. Results: Musical ear syndrome started 1 day after implantation. It ceased immediately after cochlear explantation, but reappeared 3 months later. Conclusions: Several types of factors seem to determine whether a musical ear syndrome is present or not. We propose to differentiate between triggers, modifiers, and conditions, which determine a base vulnerability. Vulnerability seems to be increased by auditory deprivation and by habitual retrieval of music from memory. Cochlear implantation or explantation seems to act as triggers. The proposed framework may help to stimulate reporting of more potentially relevant factors in future case reports on musical ear syndrome, and ultimately to help to understand this condition better. Address correspondence and reprint requests to Martin Kompis, M.D., Ph.D., Department of ENT, Head and Neck Surgery, Inselspital, University of Berne, CH—3010 Bern, Switzerland; E-mail: martin.kompis@insel.ch The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

High Altitude Alternobaric Facial Palsy: Case Series and Systematic Review of the Literature Background: Alternobaric facial palsy (AFP) is a rare phenomenon which occurs in patients with Eustachian tube dysfunction, a dehiscent facial canal, and subsequent compression induced ischemic neuropraxia of the facial nerve upon exposure to atmospheric pressure changes. There are few documented cases of AFP and most relate to underwater diving. There is limited understanding in the literature of AFP in the setting of high altitude, leading to a potential for misdiagnosis and inappropriate management. Objective: We present two cases of transient, recurrent, unilateral facial palsy at high altitude and perform a systematic review of the available literature. Data Sources: Full-text articles indexed to Medline, EMBase, and PubMed, and associated reference lists. Data Extraction: Data was extracted into standardized data extraction forms. Data Synthesis: Binomial proportions and Fischer's exact test were used to analyze sex distribution and relationship between sex and side of palsy, and number of episodes experienced. Methods: Systematic review using PRISMA guidelines with meta-analysis. Results: We identified 19 cases in the literature relating to AFP in patients at high altitude and present two new cases. Conclusion: AFP is an uncommon but important diagnosis. We present two cases and systematically review the literature to discuss the diagnosis and management of AFP. Address correspondence and reprint requests to Benjamin Cumming, M.D., Otolaryngology, Head and Neck Surgery Research Group, Department of Otolaryngology, Head and Neck Surgery, Prince of Wales Hospital, Barker St, Randwick NSW 2031, Australia; E-mail: bencumming@me.com The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company