Factors Influencing Pediatric Cochlear Implant Outcomes: Carolina Sibling Study Objective: To determine the correlation between speech perception performance between pediatric sibling pairs with severe to profound sensory hearing loss receiving cochlear implants, and in cases of discordance in performance, determine which variables negatively impacted performance. Study Design: Retrospective chart review. Setting: Tertiary academic referral center. Subjects: Eighty-nine pediatric subjects, 43 sibling groups, under the age of 18 with severe to profound sensory hearing loss who received a cochlear implant with a sibling who also received a cochlear implant. Intervention: Cochlear implantation. Main Outcome Measures: Speech perception scores, consonant-nucleus- consonant score. Results: A statistically significant correlation was found between speech perception performance of pediatric siblings. Depth of insertion is positively correlated with better speech perception in siblings with discordant results. There was no significant relationship with either electrode type, unilateral/bilateral status, or age of implantation. Conclusion: Pediatric siblings have a high correlation in speech perception outcomes following cochlear implantation, suggesting family environment plays a strong role. In circumstances in which outcomes between siblings are substantially different, greater depth of implant insertion is correlated with better consonant-nucleus- consonant word scores. Address correspondence and reprint requests to Kevin D. Brown, M.D., Ph.D., 170 Manning Drive, CB #7070, Physicians Office Building, Room G190A, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7070; E-mail: kevin_d_brown@med.unc.edu Dr. K.D.B. had a temporary assignment on the Med-El Surgical Advisory Board. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Occipital and Cerebellar Theta Burst Stimulation for Mal De Debarquement Syndrome Background: Individuals with Mal de Debarquement syndrome (MdDS) experience persistent oscillating vertigo lasting for months or years. Transcranial magnetic stimulation (TMS) can modulate the motion perception of MdDS. Materials and Methods: Twenty-six TMS naive individuals received single administrations of continuous theta burst stimulation (cTBS) over the occipital cortex, cerebellar vermis, and lateral cerebellar hemisphere, in randomized order. A 0–100 point Visual Analogue Scale was used to assess acute changes in oscillating vertigo severity after each session. Repeated treatments were given over the target that led to the most acute reduction in symptoms. All treatments were performed with neuronavigation using the participant's own brain MRI. The Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS) were assessed weekly at four pretreatment and six posttreatment time points. Results: Twenty participants chose either the occipital cortex (11) or cerebellar vermis (9) targets as most effective in reducing the oscillating vertigo; one chose lateral cerebellar hemisphere; five chose none. After 10 to 12 sessions of 1,200 pulses over the target of choice, 19 of 25 treatment completers noted ≥ 25% reduction, 12 of 25 ≥50% reduction, and 8 of 25 ≥75% reduction in oscillating vertigo intensity. A one-way repeated measures ANOVA of DHI, MBRS, and HADS scores before and after treatment showed significant reductions in DHI, MBRS, and the HADS Anxiety subscore immediately after treatment with most improvement lasting through posttreatment week 6. There were no significant Depression subscore changes. Participants who had chosen vermis stimulation had comparatively worse balance at baseline than those who had chosen occipital cortex stimulation. Conclusion: cTBS over either the occipital cortex or cerebellar vermis is effective in reducing the oscillating vertigo of MdDS acutely and may confer long-term benefits. Sustained improvement requires more frequent treatments. Address correspondence and reprint requests to Yoon-Hee Cha, M.D., 6655 South Yale Avenue, Tulsa, OK 74136; E-mail: ycha@laureateinstitute.org This work was supported by the Laureate Institute for Brain Research, the William K. Warren Foundation, an equipment and study grant from the MdDS Balance Disorders Foundation, the Springbank Foundation, an award through NSF EPSCoR RII Track-2 #1539068, and NIH/NIGMS grant P20 GM121312. All authors were involved in the design, data collection, analysis, and manuscript preparation. 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 (www.jcraniofacialsurgery.com). Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Lessons From an Analysis of Newborn Hearing Screening Data for Children With Cochlear Implants Objectives: The aims of the study are to identify the limitations of the current newborn hearing screening (NHS) programs and provide recommendations for better protocols. Study Design: Retrospective analysis. Setting: Tertiary referral center. Patients: The study participants were 185 children who received cochlear implants (CIs) at ≤5 years of age. Interventions: Therapeutic and rehabilitative. Main Outcome Measures: The results of NHS, screening tools used, age, and hearing thresholds at which hearing loss was confirmed, causes of the hearing loss, age of CI insertion, aided pure-tone audiogram findings, and language development level were analyzed. Results: NHS data was available for 109 children, and 24 patients (22.0%) had passed NHS for both ears. Hearing loss was confirmed considerably later in children who had passed NHS than in children who were referred for further evaluation (p < 0.01). The most common cause for hearing loss in the NHS-pass group was SLC26A4 mutations (41.7%). Patients in the NHS-pass group received CIs considerably later than those in the NHS-referred group (p < 0.01). Among patients with SLC26A4 mutations, the language development level was significantly lower in the NHS-pass group than in the NHS-referred group (p < 0.01). Conclusions: Careful counseling regarding NHS results is necessary for parents to understand that the absence of hearing loss at birth does not mean that the child will not develop hearing loss later in life. Genetic testing for SLC26A4 mutations may be necessary in regions with a high incidence of these mutations, such as East Asia. Address correspondence and reprint requests to Jae Young Choi, M.D., Ph.D., Department of Otorhinolaryngology, Yonsei University College of Medicine, Severance Hospital, Yonsei University Health System, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea; E-mail: jychoi@yuhs.ac This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1C1C1006341) to J.M.L. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

The Antrum–Malleus–Tegmen Score: A Pilot Study Assessing Preoperative Radiographic Predictors for Transcanal Endoscopic Cholesteatoma Dissection Objective: Identify features on computed tomography (CT) that predict mastoidectomy conversion (MC) during transcanal endoscopic ear surgery (TEES). Study Design: Retrospective case-control. Setting: University otology practice. Patients: Consecutive patients with cholesteatoma. Intervention: TEES cholesteatoma dissection versus those requiring MC. Main Outcome Measures: Antrum opacification, depth of scutum involvement, and erosion of the mastoid trabeculae, ossicular chain, and tegmen were evaluated. Univariable and multivariable regression analysis was performed. The Antrum–Malleus–Tegmen (AMT) score was created using receiver operating characteristic curves to assess feasibility of performing TEES for cholesteatoma dissection. Results: There were 39 TEES and 19 MC cases. Groups had similar age (median 28.5 yr), gender, laterality, and revision surgery status. Median surgical time for MC cases was longer than TEES (231 min vs. 171 min, p < 0.001). Radiographic predictors of MC by multivariable regression included antrum opacification (p = 0.036), malleus erosion (p = 0.044), and tegmen erosion (p = 0.023). The AMT score predicted the feasibility of TEES without MC with a sensitivity of 90% and specificity of 75% when ≥2 of the following conditions were met on preoperative CT: intact tegmen, intact malleus, and absence of antrum opacification. Conclusions: An aerated antrum, intact malleus, and intact tegmen suggest that TEES cholesteatoma dissection without the need for mastoidectomy is highly likely. A score of ≥2 on the AMT score predicts this with a positive predictive value of 88% and negative predictive value of 78%. Address correspondence and reprint requests to Anthony M. Tolisano, M.D., Department of Otolaryngology–Head and Neck Surgery, University of Texas Southwestern Medical Center, 2001 Inwood Blvd, Dallas, TX 75390-9035; E-mail: Anthony.tolisano@utsouthwestern.edu This project was approved and in compliance with University of Texas Southwestern Medical Center IRB STU 012013-017. This manuscript was presented as an oral presentation (1150-Radiographic Predictors of Conversion from Endoscopic to Open Treatment of Cholesteatoma) at the 2018 AAO-HNS annual meeting. The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

The Feasibility to Isolate and Expand Tympanic Membrane Squamous Epithelium Stem Cells From Scarred Perforation Margins Hypothesis: The scarred rim of chronic tympanic membrane (TM) perforation contains keratinocytes with potential for regeneration while maintaining their morphological and genetic characteristics. Background: The squamous epithelium of the TM has a good regeneration capacity. Successful isolation and expansion of human TM keratinocytes (hTMKR) was reported from a full, en-bloc, healthy TM. Methods: Trimmed margins of the TM perforation (harvested during tympanoplasty) underwent enzymatic digestion (collagenase or trypsin) and were seeded either with serum-containing medium (SCM) or keratinocyte serum-free medium (KSFM) and progenitor cell growth medium (PR) (KSFM:PR, 1:1). Gene expression analysis by real-time qRT-PCR was used to compare between human TM cells derived from scarred perforation margins (hTMKR), normal human skin keratinocytes (NhSKR), and human fibroblasts. Results: Twelve patients were included in the study. In 9 of 12 cases (75%) single-cell isolation with fibroblastic or epithelial cell morphology (or both) was achieved. Cells seeded with KSFM:PR yielded epithelial morphology (hTMKR) while SCM culturing resulted in a fibroblastic morphology (hTMFib). Gene expression analysis revealed significant higher expression of VCAN (p = 0.002) and FOXC2 (p = 0.015) at the mRNA levels (normal hTMKR markers) in hTMKR compared to NhSKR. In addition, a comparison of gene expression between hTMKR and hTMFib revealed significantly higher levels of both VCAN (p = 0.045) and SLC6A14 (p = 0.036) among hTMKR. Conclusion: For the first time, we developed a protocol to isolate hTMKR from scarred TM perforation margins. Furthermore, we succeeded in achieving tissue expansion that preserved the characteristic of healthy TM cells. This study bridges “regenerative medicine” approach with clinical and surgical objectives. Address correspondence and reprint requests to Doron Sagiv, M.D., Department of Otolaryngology, Head & Neck Surgery, Sheba Medical Center, Tel Hashomer 52621, Israel; E-mail: doron.sagiv1@gmail.com B.D. and D.O. contributed equally to this manuscript. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Long-term Outcomes of Balloon Dilation for Persistent Eustachian Tube Dysfunction Objective: To gather long-term follow-up data on the efficacy of balloon dilation for treating patients with persistent Eustachian tube dysfunction (ETD). Study Design: Extended follow-up study of the treatment arm of a prospective, multicenter, randomized controlled trial. Setting: Tertiary care academic center and private practice. Patients: Patients diagnosed with medically refractory persistent ETD. Interventions: Balloon dilation of the Eustachian tube. Main Outcome Measures: The endpoints were the mean change from baseline in the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) score, revision dilation rate, changes in assessments of middle ear function, and patient satisfaction. Results: A total of 47 participants enrolled in the extended follow-up study. Mean follow-up was 29.4 months (range, 18–42 mo). There was a statistically significant mean (SD) change from baseline in the overall ETDQ-7 score (–2.5 ± 1.2; p < 0.0001). A reduction of one or more in their overall ETDQ-7 score was observed by 93.6% (44/47) participants. The revision dilation rate was 2.1% (1/47). Among participants with abnormal baseline middle ear assessments, 76.0% had normalized tympanic membrane position (p < 0.0001), 62.5% had normalization of tympanogram type (p < 0.001), and 66.7% had positive Valsalva maneuvers (p < 0.0001). Participant satisfaction was 83.0% at long-term follow-up. Conclusions: Balloon dilation results in durable improvements in symptoms and middle ear assessments for patients with persistent Eustachian tube dysfunction at mean follow-up of longer than 2 years. Address correspondence and reprint requests to Jeffrey L. Cutler, M.D., Colorado Sinus Institute, 850 Harvard E. Ave, Suite 505, Denver, CO 80210; E-mail: jeffrey.cutler@hotmail.com Entellus Medical designed and sponsored this study. Conflicts of Interest: E.M.O., an employee of Entellus Medical, Inc., assisted with the initial draft of the manuscript, editing, and preparation for submission. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Anatomical Correlates and Surgical Considerations for Localized Therapeutic Hypothermia Application in Cochlear Implantation Surgery Hypothesis: Application of localized, mild therapeutic hypothermia during cochlear implantation (CI) surgery is feasible for residual hearing preservation. Background: CI surgery often results in a loss of residual hearing. In preclinical studies, local application of controlled, mild therapeutic hypothermia has shown promising results as a hearing preservation strategy. This study investigated a suitable surgical approach to deliver local hypothermia in patients utilizing anatomical and radiologic measurements and experimental measurements from cadaveric human temporal bones. Methods: Ten human cadaveric temporal bones were scanned with micro-computed tomography and anatomical features and measurements predicting round window (RW) visibility were characterized. For each bone, the standard facial recess and myringotomy approaches for delivery of hypothermia were developed. The St. Thomas Hospital (STH) classification was used to record degree of RW visibility with and without placement of custom hypothermia probe. Therapeutic hypothermia was delivered through both approaches and temperatures recorded at the RW, RW niche, over the lateral semicircular canal and the supero-lateral mastoid edge. Results: The average facial recess area was 13.87 ± 5.52 mm2. The introduction of the cooling probe through either approach did not impede visualization of the RW or cochleostomy as determined by STH grading. The average temperatures at RW using the FR approach reduced by 4.57 ± 1.68 °C for RW, while using the myringotomy approach reduced by 4.11 ± 0.98 °C for RW. Conclusion: Local application of therapeutic hypothermia is clinically feasible both through the facial recess and myringotomy approaches without limiting optimal surgical visualization. Address correspondence and reprint requests to Suhrud M. Rajguru, Ph.D., University of Miami Ear Institute, 1095 NW 14 Terrance, Lois Pope Life Center, Room 4-25, Miami, Florida 33134; E-mail: s.rajguru@miami.edu E.P. and A.V.E. have equal contribution. This work was supported by a Research Grant from Cochlear, R01 DC01379801A1 and a pilot award from National Center For Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002736, Miami Clinical and Translational Science Institute. S.M.R. and C.K. are named inventors on intellectual property related to the design of hypothermia system and probe discussed here. The authors declare no competing financial interests related to the findings presented. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Hearing Preservation With the Use of Flex20 and Flex24 Electrodes in Patients With Partial Deafness Objective: To evaluate the impact of electrode length on hearing preservation (HP) in Partial Deafness Treatment–Electrical Complement (PDT-EC) subjects. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Twenty-three PDT-EC patients (with preoperative air-conduction thresholds ≤30 dB up to 500 Hz) were divided into two groups: Flex20 electrode (Med-EL GmbH, Innsbruck, Austria) (12 patients) and Flex24 electrode (Med-EL GmbH, Innsbruck, Austria) (11 patients). Interventions: All participants were subjected to minimally invasive cochlear implantation using the round window approach. Main Outcome Measure(s): Pure tone audiometry (125–8000 Hz) was performed preoperatively and at 1, 6, 12, and 24 months postoperatively. HP was established using the HEARRING group formula. Speech understanding was assessed preoperatively and at 12 and 24 months postoperatively. Results: Analysis of HP for every individual indicates that more than half the patients with Flex20 and Flex24 had complete HP at 6 months follow-up. None of the patients from either group had complete loss of hearing. At activation, average air-conduction thresholds for low frequencies (125–500 Hz) were slightly better for the short electrode (M = 29.03) than for the long (M = 39.10) but the difference was not statistically significant (p = 0.067). The effect of electrode (Flex20 versus Flex24) was not significant in terms of pure tone audiometry and speech recognition at long-term follow-up. Conclusions: In the early postoperative period, complete HP was possible in a majority of patients from both groups, but slightly better HP outcomes were achieved by Flex20. In the long term, the length of the electrodes does not affect the degree of HP or speech understanding. Address correspondence and reprint requests to Piotr H. Skarzynski, Ph.D., M.D., M.S., Mokra 17 Street, 05-830 Kajetany, Poland; E-mail: p.skarzynski@ifps.org.pl No other benefits were received. 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). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

Endre Hőgyes (1847–1906), Forgotten Father of the Vestibulo-Ocular Reflex Objective: Throughout the history of vestibular research, the discovery of the vestibulo-ocular reflex in 1881 by Endre Hőgyes (1847–1906) is rarely mentioned. The aim of this study is to review Hőgyes’ vestibular research articles, all originally written in Hungarian and emphasize their epoch-making content. Main Data Sources: Hőgyes’ vestibular publications, originally written in Hungarian, which describe various eye movements of the rabbit in response to vestibular stimulation by rotation about three axes. Results: Hőgyes was the first to use a three-axis turntable on an experimental animal, in this case a rabbit. He found that depending on the plane of rotation, different types of binocular eye movements were produced. He then demonstrated by destructive and excitatory experiments, the anatomical pathways and the physiological function producing this phenomenon. Ultimately, he explained the exact connections between the inner ear labyrinth and certain muscle contractions during eye movements. He identified this pathway as the “associating center of the ocular movements,” later defined as the vestibulo-ocular reflex. Hőgyes’ discovery was only superficially noted during his lifetime and ignored after his death. Conclusion: Hőgyes was the first to demonstrate the vestibulo-ocular reflex. He was forgotten during the ensuing 140 years probably because his articles were appeared only in Hungarian and because a short time later, Róbert Bárány's award of the Nobel Prize overshadowed many of Bárány's predecessors and contemporaries, including Hőgyes and relegated them to the background. Address correspondence and reprint requests to László T. Tamás, M.D., 9028, Győr, Vak Bottyán u.14/A, Hungary; E-mail: ltamas@gyor.net Dr. L.T.T. and Dr. A.M. helped in data collection, analysis, and interpretation, critically reviewing and editing the manuscript. The authors disclose no conflicts of interest. Copyright © 2019 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company