Long-term Outcomes for the Treatment of Paragangliomas in the Upfront, Adjuvant, and Salvage Settings With Stereotactic Radiosurgery and Intensity-modulated Radiotherapy Objective: To analyze local control (LC) and toxicity rates between stereotactic radiosurgery (SRS) and intensity-modulated radiotherapy (IMRT) in relation to reported surgical rates in the treatment of paragangliomas (PG) in the upfront, adjuvant, and salvage settings, and to explore factors affecting tumor size reduction, toxicity rates, and symptom control. Study Design: Retrospective cohort analysis. Setting: Tertiary referral center. Patients and Interventions: Thirty patients treated with either linear accelerator-based SRS or IMRT in the definitive, planned adjuvant, or unplanned salvage postsurgery settings. Main Outcome Measures: Local control, toxicities, symptom control, tumor size reduction, and factors affecting each. Results: Median follow-up was 4.16 years. LC rates were 100%. Acute grade >3 toxicity rate was 6.7%, 86.7% of tumors had a reduction in volume, and 76.7% of patients had improvement in at least one tumor-induced symptom by last follow-up. Larger tumor size at presentation and longer time to last follow-up were significantly associated with greater tumor size reduction on multivariate analysis. Conclusions: SRS and IMRT are safe and effective treatment for PG with high efficacy and low morbidity rates in the upfront, planned adjuvant, and unplanned salvage settings. Address correspondence and reprint requests to Anthony J. Cmelak, M.D., Professor, Senior Medical Director of Radiation Oncology Satellites, Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Avenue, B1003 Preston Research Building, Nashville, TN 37232-5671; E-mail: anthony.cmelak@vumc.org; Joshua Lee Anderson, B.S., Vanderbilt University School of Medicine, Nashville, TN 37232; E-mail: joshandy40@gmail.com The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Intratympanic Treatment in Menière's Disease, Efficacy of Aminoglycosides Versus Corticosteroids in Comparison Studies: A Systematic Review Objective: To compare the functional outcomes and complications of intratympanic gentamicin (ITG) versus intratympanic corticosteroids (ITC) in Menière's disease. Data Sources: An electronic search was conducted in the Cochrane Library, PubMed, and Embase databases on February 3, 2019. Articles written in English, Dutch, German, French, or Turkish language were included. Study Selection: Study inclusion criteria were: 1) patients diagnosed with definite Menière's disease according to the criteria of the American Academy of Otolaryngology-Head and Neck Surgery, 2) treated with ITG or ITC in a comparison study, and 3) reported subjective and objective outcomes concerning Menière's disease. Data Extraction: The quality of eligible studies was assessed according to an adjusted version of the Cochrane Risk of Bias tool. The extracted data were study characteristics (study design, publication year, and number of relevant patients), patient's characteristics (sex and age), disease characteristics (uni or bilateral and duration of Menière's disease), treatment protocol, and different therapeutic outcomes (vertigo, tinnitus, aural fullness, and hearing loss). Data Synthesis: A total of eight articles were included for data extraction and analysis. For subjective outcomes, ITG was slightly favored compared to intratympanic corticosteroids. This was significant only in three studies (p < 0.05). For objective outcomes and complications, no significant differences were seen. Conclusions: The result of this systematic review shows some benefit of ITG over ITC for subjective outcomes and no difference regarding objective outcomes or complication rate. However, this superiority of ITG is rather weak. Both interventions can be effectively and safely used in controlling Menière's disease in acute situations. Address correspondence and reprint requests to Hans G.X.M. Thomeer, Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Utrecht, Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; E-mail: H.G.X.M.Thomeer@umcutrecht.nl The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Sex-Based Differences in Hearing Loss: Perspectives From Non-Clinical Research to Clinical Outcomes Introduction: It is estimated over 466 million people worldwide have disabling hearing loss, and untreated hearing loss is associated with poorer health outcomes. The influence of sex as a biological variable on hearing loss is not well understood, especially for differences in underlying mechanisms which are typically elucidated through non-clinical research. Although the inclusion of sex as a biological variable in clinical studies has been required since 1993, sex reporting has only been recently mandated in National Institutes of Health funded non-clinical studies. Objective: This article reviews the literature on recent non-clinical and clinical research concerning sex-based differences in hearing loss primarily since 1993, and discusses implications for knowledge gaps in the translation from non-clinical to clinical realms. Conclusions: The disparity between sex-based requirements for non-clinical versus clinical research may inhibit a comprehensive understanding of sex-based mechanistic differences. Such disparities may play a role in understanding and explaining clinically significant sex differences and are likely necessary for developing robust clinical treatment options. Address correspondence and reprint requests to Katrina M. Schrode, Ph.D., Department of Otolaryngology–Head & Neck Surgery, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205; E-mail: kschrod1@jhmi.edu This manuscript was supported by the Acoustical Society of America James E. West Fellowship to D.F.V., the David M. Rubenstein Fund for Hearing Research to A.M.L., and NIH grants R01 DC016641 DC017620 to A.M.L. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Replicating Skull Base Anatomy With 3D Technologies: A Comparative Study Using 3D-scanned and 3D-printed Models of the Temporal Bone Hypothesis: 3D technologies, including structured light scanning (SLS), microcomputed tomography (micro-CT), and 3D printing, are valuable tools for reconstructing temporal bone (TB) models with high anatomical fidelity and cost-efficiency. Background: Operations involving TB require intimate knowledge of neuroanatomical structures—a demand that is currently met through dissection of limited cadaveric resources. We aimed to document the volumetric reconstruction of TB models using 3D technologies and quantitatively assess their anatomical fidelity. Methods: In the primary analysis, 14 anatomical characteristics of right-side TB from 10 dry skulls were measured. Each skull was 3D-scanned using SLS to generate virtual models, which were measured using mesh processing software. Metrics were analyzed using mean absolute differences and one-sample t tests with Bonferroni correction. In the secondary analysis, an individualized right-side TB specimen (TBi) was 3D-scanned using SLS and micro-CT, and 3D-printed on a stereolithography printer. Measurements of each virtual and 3D-printed model were compared to measurements of TBi. Results: Significant differences between the physical skulls and virtual models were observed for 11 of 14 parameters (p < 0.0036), with the greatest mean difference in the length of petrous ridge (2.85 mm) and smallest difference in the diameter of stylomastoid foramen (0.67 mm). In the secondary analysis, greater mean differences were observed between TBi and virtual models than between TBi and 3D-printed models. Conclusion: For the first time, our study provides quantitative measurements of TB anatomy to demonstrate that 3D technologies can facilitate individualized and highly accurate reconstructions of TB, which may benefit anatomy education, clinical training, and preoperative planning. Address correspondence and reprint requests to Roberto Rodriguez Rubio, M.D., Assistant Professor, Departments of Neurological Surgery and Otolaryngology – Head and Neck Surgery, University of California, San Francisco, CA, Director, Skull Base and Cerebrovascular Laboratory, University of California, San Francisco, 513 Parnassus Ave HSE 817 Box 0112, San Francisco, CA 94143; E-mail: luis.rodriguezrubio@ucsf.edu Part of this work was presented at the 29th Annual North American Skull Base Society Meeting in Orlando, Florida, February 16, 2019. The authors disclose no conflicts of interest. 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

Duration of Processor Use Per Day Is Significantly Correlated With Speech Recognition Abilities in Adults With Cochlear Implants Objective: Quantify the relationship between average hours of processor use per day and measures of speech recognition in post-lingually deafened adults with cochlear implants. Setting: Cochlear implant (CI) program at a tertiary medical center. Patients: Three hundred adult (mean age = 64, 130 women) CI users were included. Main Outcome Measures: Correlation analyses were completed for CI-aided speech recognition (Consonant-Nucleus-Consonant [CNC] monosyllables and AzBio sentences) at approximately 12 months post-implantation and average hours of processor use per day, which was extracted from the CI programming software. Results: Average processor use was 10.2 hours per day (range, 0.1–22.7), and average speech recognition scores were 49.9 and 61.7% for CNC and AzBio sentence recognition, respectively. We found a strong, significant correlation between hours of processor use per day and consonant-nucleus-consonant (CNC) word recognition (rs = 0.61, p < 0.0001) and AzBio sentence recognition (rs = 0.56, p < 0.0001). Conclusions: Results suggest that highest speech recognition outcomes are correlated with greater than 10 hours of CI use per day. Further research is needed to assess the causal link between daily CI use and speech recognition abilities. Address correspondence and reprint requests to Jourdan T. Holder, Au.D., Department of Hearing and Speech Sciences, 1215 21st Avenue South, Medical Center East, South Tower, #9302, Nashville, TN 37232-8605; E-mail: jourdan.t.holder@vumc.org Financial material & support: NIH R01 DC13117; PI: René H. Gifford, PhD. INSITUTIONAL REVIEW BOARD: IRB# 190958. R.G.: Advisory board for Advanced Bionics, Cochlear, and Frequency Therapeutics. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Anatomical and Functional Consequences of Microneedle Perforation of Round Window Membrane Hypothesis: Microneedles can create microperforations in the round window membrane (RWM) without causing anatomic or physiologic damage. Background: Reliable delivery of agents into the inner ear for therapeutic and diagnostic purposes remains a challenge. Our novel approach employs microneedles to facilitate intracochlear access via the RWM. This study investigates the anatomical and functional consequences of microneedle perforations in guinea pig RWMs in vivo. Methods: Single three-dimensional-printed, 100 μm diameter microneedles were used to perforate the guinea pig RWM via the postauricular sulcus. Hearing was assessed both before and after microneedle perforation using compound action potential and distortion product otoacoustic emissions. Confocal microscopy was used ex vivo to examine harvested RWMs, measuring the size, shape, and location of perforations and documenting healing at 0 hours (n = 7), 24 hours (n = 6), 48 hours (n = 6), and 1 week (n = 6). Results: Microneedles create precise and accurate perforations measuring 93.1 ± 29.0 μm by 34.5 ± 16.8 μm and produce a high-frequency threshold shift that disappears after 24 hours. Examination of perforations over time demonstrates healing progression over 24 to 48 hours and complete perforation closure by 1 week. Conclusion: Microneedles can create a temporary microperforation in the RWM without causing significant anatomic or physiologic dysfunction. Microneedles have the potential to mediate safe and effective intracochlear access for diagnosis and treatment of inner ear disease. Address correspondence and reprint requests to Anil K. Lalwani, M.D., Division of Otology, Neurotology, and Skull Base Surgery, Department of Otolaryngology—Head and Neck Surgery, Columbia University College of Physicians and Surgeons, 180 Fort Washington Avenue, Harkness Pavilion, 8th Floor, New York, NY 10032; E-mail: anil.lalwani@columbia.edu E.S.O., J.W.K., and A.K.L. are co-senior authors. Research was funded by the National Institutes of Health (NIH) National Institute on Deafness and Other Communication Disorders with award number R01DC014547. Dr. A.K.L. is on the Medical Advisory Board of Advanced Bionics. The authors disclose no other conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Pregnancy Does Not Increase the Risk of Bell's Palsy: A National Cohort Study Objectives: The objective of this study was to compare the incidence of Bell's palsy between women during pregnancy or postpartum periods and non-pregnant/non-postpartum women (controls). Methods: Using the national cohort from the Korean Health Insurance Review and Assessment Service, pregnant/postpartum participants (63,264) and control participants (126,528) were matched in a 1:2 ratio based on age, income, region of residence, and medical history. The incidence of Bell's palsy in both groups was measured from pregnancy to 1 year postpartum. Results: Among the 63,264 pregnant/postpartum participants, 20 were diagnosed with or treated for Bell's palsy during pregnancy, and 38 during postpartum periods. The annual incidence of Bell's palsy per 100,000 women during pregnancy was 43.4 in the patient group and 80.2 in the control group (p < 0.05), and that during postpartum periods was 60.1 the patient group and 50.6 in the control group (p > 0.05). Conclusion: The annual incidence of Bell's palsy was not increased in pregnant women relative to that in the control. Address correspondence and reprint requests to Jiwon Chang, M.D., Ph.D., Department of Otolaryngology–Head & Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 948-1 Daerim 1-dong, Yeongdeungpo-gu, Zip: 150-950, Seoul, Republic of Korea; E-mail: brune77@naver.com This work was supported in part by a research grant (NRF-2015-R1D1A1A01060860, NRF- 2015R1C1A1A01054397) from the National Research Foundation of Korea. Financial Disclosures: None. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Current Volumetric Models Overestimate Vestibular Schwannoma Size Following Stereotactic Radiosurgery Objective: Accurate volume assessment is essential for the management of vestibular schwannoma after stereotactic radiosurgery (SRS). A cuboidal approximation for volume is the standard surveillance method; however, this may overestimate tumor volume. We sought to evaluate several volumetric models and their suitability for post-SRS surveillance. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: We evaluated 54 patients with vestibular schwannoma before and after SRS. Intervention(s): Gold-standard volumes were obtained by a radiation oncologist using contouring software. Volume was also calculated by cuboidal, ellipsoidal, and spherical formulae using tumor diameters obtained by a neuroradiologist. Main Outcome Measure(s): Percent error (PE) and absolute percent error (APE) were calculated. Paired t test evaluated bias, and the Bland–Altman method evaluated reproducibility. Linear regression evaluated predictors of model error. Results: All models overestimated volume compared with the gold standard. The cuboidal model was not reproducible before SRS (p < 0.001), and no model was reproducible after SRS (cuboidal p < 0.001; ellipsoidal p = 0.02; spherical p = 0.02). Significant bias was present before SRS for the cuboidal model (p < 0.001), and post-SRS for all models [cuboidal (p < 0.001), ellipsoidal (p < 0.02), and spherical (p = 0.005)]. Model error was negatively associated with pretreatment volume for the cuboidal (PE p = 0.03; APE p = 0.03), ellipsoidal (PE p = 0.03; APE p = 0.04), and spherical (PE p = 0.02; APE p = 0.03) methods and lost linearity post-SRS. Conclusions: The standard cuboidal practice for following vestibular schwannoma tumor volume after SRS overestimates size. Ellipsoidal and spherical estimations have improved performance but also overestimate volume and lack reliability post-SRS. The development of other volumetric models or application of contouring software should be investigated. Address correspondence and reprint requests to Anthony J. Cmelak, M.D., Professor, Senior Medical Director of Radiation Oncology Satellites, Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building, Rm B-1003, Nashville, TN 37232-5671; E-mail: anthony.cmelak@vumc.org All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was waived by the IRB due to minimal risk. Mohamed H. Khattab receives research funding from Varian Medical Systems and Brainlab. Alejandro Rivas is a consultant for Advanced Bionics, Med-El, Cochlear Corporation, Cook Medical, Grace Medical, and Stryker. Albert Attia receives funding from Brainlab, AstraZeneca, and Novocure. The remaining authors have no conflicts of interest to disclose. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Incidental Effect of Long-Term Tacrolimus Treatment on Sporadic Vestibular Schwannoma Volume Shrinkage and Clinical Improvement Objective: We describe the effect of long-term tacrolimus delivery on sporadic vestibular schwannoma (VS). Patient: A 48-year-old woman who was diagnosed a right VS. Intervention: Long-term tacrolimus delivery following liver transplant. Main Outcome Measures: Clinical examination, audiometric test, and gadolinium-contrasted magnetic resonance imaging. Results: During the reported follow-up period, the patient felt hearing improvement especially in noisy environment. This was consistent with a clear audiometric improvement. Over a 26 months follow-up period, we noticed a 50% volume regression and a 40% decrease in the intensity of enhancement of the tumor after gadolinium injection. Conclusion: Tacrolimus, an immunosuppressant used to prevent rejection in organ transplant, could lead to VS volume shrinkage and hearing improvement. Tacrolimus could be an interesting new therapeutic weapon, especially for VS in Neurofibromatosis type 2. Address correspondence and reprint requests to Marion Montava, M.D., Ph.D., Department of Otorhinolaryngology–Head and Neck Surgery, Conception Hospital, Aix-Marseille University, 147 Boulevard Baille, 13005 Marseille, France; E-mail: marion.montava@ap-hm.fr The authors do not have any conflicts of interest or financial disclosure to declare. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Functional Head Impulse Test With and Without Optokinetic Stimulation in Subjects With Persistent Postural Perceptual Dizziness (PPPD): Preliminary Report Objective: Persistent postural perceptual dizziness (PPPD) is a clinical condition characterized by unsteadiness present on most days for a period of at least 3 months. The aim of our work was to assess vestibular function, the role of anxiety, and possible interactions between visual and vestibular systems in patients with PPPD. Study Design: Cross-sectional prospective study. Setting: Tertiary referral center. Patients: Twenty-five PPPD patients. Interventions: Clinical history was collected before examination; vestibular function was assessed through bedside examination, video and functional head impulse test (video-HIT, f-HIT). The latter test was based on having the patient identify an optotype displayed on a computer screen during passive head rotations. The test was repeated while optokinetic stimulation (OKS) was given on the screen. Results were compared with those of 25 controls. State and trait anxiety levels were measured with the State-Trait Anxiety Inventory (STAI) questionnaire. Anxiety before and after vestibular examination was assessed using a VAS scale. Main Outcome Measure: Results of video and functional HIT with and without OKS. Results: Video-HIT and f-HIT showed normal values in all subjects. f-HIT with OKS provoked more reading errors in patients than in controls. The interaction of group per time detected different decreasing trends between the two groups (p = 0.0002). Patients presented a reduction in anxiety levels after examination. Nine patients fulfilled diagnostic criteria for vestibular migraine, eight of whom presented nystagmus either to positional tests or vibration test. Only anxiety levels before testing were predictive of worsening of f-HIT with optokinetic stimulation (p = 0.0007). Conclusions: Our data support the hypothesis that increased anxiety may play a role in visuo-vestibular interactions; moreover, they are not inconsistent with the hypothesis that OKS might provoke a “threatening effect,” leading to gaze bias during examination. Address correspondence and reprint requests to Roberto Teggi, M.D., San Raffaele Hospital, via Olgettina 60, 20132 Milan, Italy; E-mail: teggi.roberto@hsr.it The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company