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Series Editor: Robert T Sataloff

 

SATALOFF'S COMPREHENSIVE TEXTBOOK OF OTOLARYNGOLOGY HEAD AND NECK SURGERY MD DMA FACS

OTOLOGY/NEUROTOLOGY/ SKULL BASE SURGERY

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Series Editor: Robert T Sataloff

 

SATALOFF'S COMPREHENSIVE TEXTBOOK OF OTOLARYNGOLOGY HEAD AND NECK SURGERY MD DMA FACS

OTOLOGY/NEUROTOLOGY/ SKULL BASE SURGERY Vol. 1

Volume Editor

Anil K Lalwani MD Professor and Vice Chair for Research Director, Division of Otology, Neurotology and Skull Base Surgery Director, Columbia Cochlear Implant Program Department of Otolaryngology—Head and Neck Surgery Columbia University College of Physicians and Surgeons New York, New York, USA

The Health Sciences Publisher New Delhi | London | Philadelphia | Panama

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Jaypee Brothers Medical Publishers (P) Ltd

Headquarters Jaypee Brothers Medical Publishers (P) Ltd. 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 E-mail: [email protected] Overseas Offices J.P. Medical Ltd. 83, Victoria Street, London SW1H 0HW (UK) Phone: +44-20 3170 8910 Fax: +44(0)20 3008 6180 E-mail: [email protected]

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Jaypee Medical Inc. The Bourse 111 South Independence Mall East Suite 835, Philadelphia, PA 19106, USA Phone: +1 267-519-9789 E-mail: [email protected]

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Jaypee Brothers Medical Publishers (P) Ltd. Bhotahity, Kathmandu, Nepal Phone: +977-9741283608 E-mail: [email protected] Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2016, Jaypee Brothers Medical Publishers

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The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. Inquiries for bulk sales may be solicited at: [email protected] Sataloff’s Comprehensive Textbook of Otolaryngology: Head and Neck Surgery: Otology/Neurotology/Skull Base Surgery (Vol. 1) First Edition: 2016 ISBN: 978-93-5152-455-7 Printed at

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Contributors Robert A Adamson MD Assistant Professor School of Biomedical Engineering Dalhousie University Halifax, Nova Scotia, Canada Sumit K Agrawal MD FRCSC Associate Professor Department of Otolaryngology— Head and Neck Surgery Western University London, Ontario, Canada Yuri Agrawal MD Assistant Professor Department of Otolaryngology— Head and Neck Surgery Johns Hopkins University School of Medicine Baltimore, Maryland, USA Art Ambrosio MD Head and Neck Surgeon at Marine Corps Base Camp Lejeune Jacksonville, North Carolina, USA Simon I Angeli MD Professor Department of Otolaryngology University of Miami Miami, Florida, USA Maris Appelbaum AuD Clinical Preceptor Department of Communication Sciences and Disorders Montclair State University Montclair, New Jersey, USA H Alexander Arts MD FACS Professor of Otolaryngology University of Michigan Ann Arbor, Michigan, USA Manohar Bance MB MSc FRCSC Professor and Head Division of Otolaryngology— Head and Neck Surgery Department of Surgery Dalhousie University Halifax, Nova Scotia, Canada

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Gregory J Basura MD Assistant Professor Department of Otolaryngology— Head and Neck Surgery Kresge Hearing Research Institute Ann Arbor, Michigan, USA Carol Bauer MD Professor/Chair Department of Surgery Division of Otolaryngology Southern Illinois University School of Medicine Springfield, Illinois, USA Joan M Besing PhD CCC-A Professor Department of Communication Sciences and Disorders Montclair State University Montclair, New Jersey, USA Jason A Beyea MD PhD FRCSC Fellow Department of Otolaryngology— Head and Neck Surgery The Ohio State University Columbus, Ohio, USA Dennis I Bojrab MD CEO and Director of Research Michigan Ear Institute Director of Skull Base Surgery Providence Hospital and Medical Centers Clinical Professor Wayne State University Farmington Hills, Michigan, USA Derald E Brackmann MD Clinical Professor of Otolaryngology— Head and Neck Surgery and Neurological Surgery University of Southern California School of Medicine Associate House Ear Clinic Board of Directors House Ear Institute Los Angeles, California, USA

Kevin D Brown MD PhD Associate Professor Department of Otolaryngology— Head and Neck Surgery University of North Carolina at Chapel Hill School of Medicine Chapel Hill, North Carolina, USA Roxanne Cano MD University of Texas Medical School Houston, Texas, USA Divya Chari MD Resident University of California, San Francisco San Francisco, California, USA Daniel H Coelho MD FACS G Douglas Hayden Associate Professor Department of Otolaryngology— Head and Neck Surgery Virginia Commonwealth School of Medicine Richmond, Virginia, USA C Eduardo Corrales MD Brigham and Women’s Instructor Associate Surgeon Department of Surgery Harvard Medical School Assistant Professor Department of Otolaryngology Massachusetts Eye and Ear Infirmary Harvard Medical School Boston, Massachusetts, USA Maura K Cosetti MD Assistant Professor Departments of Otolaryngology— Head and Neck Surgery and Neurosurgery Louisiana State University Health Sciences Center—Shreveport Shreveport, Louisiana, USA Ryan A Crane MD Resident Physician Department of Otolaryngology— Head and Neck Surgery University of Cincinnati Medical Center Cincinnati, Ohio, USA

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Karen Jo Doyle MD PhD Professor Otology and Neurotology University of California Davis Health System Department of Otolaryngology Sacramento, California, USA

Selena E Heman-Ackah MD MBA Director of Otology Neurotology, and Audiology Division of Otolaryngology Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts, USA

Robert W Eppsteiner MD University of Massachusetts Medical School Worcester, Massachusetts, USA

Michael E Hoffer MD Otolaryngology University of Miami Health System Miami, Florida, USA

Deema Fattal MD Associate Professor Director of Balance Disorders Clinic Department of Neurology University of Iowa Iowa City, Iowa, USA

Brandon Isaacson MD FACS Associate Professor Department of Otolaryngology— Head and Neck Surgery University of Texas— Southwestern Medical Center Dallas, Texas, USA

Alexander Filatov MD Department of Radiology Stony Brook University Stony Brook, New York, USA Richard A Goldman MD Assistant Professor Department of Otolaryngology— Head and Neck Surgery University of Kentucky College of Medicine Lexington, Kentucky, USA

Steven K Juhn MD Department of Otolaryngology— Head and Neck Surgery University of Minnesota Minneapolis, Minnesota, USA

Sachin Gupta MD Neurotology Fellow Department of Otolaryngology— Head and Neck Surgery, University of Texas—Southwestern Medical Center Dallas, Texas, USA

Robert W Jyung MD Associate Professor Department of Otolaryngology— Head and Neck Surgery Rutgers New Jersey Medical School Newark, New Jersey, USA

Mari Hagiwara MD Assistant Professor Department of Radiology New York University, School of Medicine New York, New York, USA

Ruwan Kiringoda MD Resident Physician Otolaryngology—Head and Neck Surgery University of California, San Francisco San Francisco, California, USA

Marlan R Hansen MD FACS Professor Departments of Otolaryngology— Head and Neck Surgery and Neurosurgery, University of Iowa Iowa City, Iowa, USA

Ilkka Kivekäs MD PhD Assistant Professor in Otolaryngology Tampere University Hospital and the University of Tampere Tampere, Finland

Mary J Hawkshaw BSN RN CORLN Research Associate Professor Department of Otolaryngology Drexel College of Medicine Philadelphia, Pennsylvania, USA

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Daniel Jethanamest MD Assistant Professor Department of Otolaryngology New York University School of Medicine New York, New York, USA

Janet Koehnke PhD Professor and Chair Department of Communication Sciences and Disorders Montclair State University Montclair, New Jersey, USA

Anil K Lalwani MD Professor and Vice Chair for Research Director Division of Otology Neurotology and Skull Base Surgery Director Columbia Cochlear Implant Program Department of Otolaryngology— Head and Neck Surgery Columbia University College of Physicians and Surgeons New York, New York, USA Lawrence R Lustig MD Howard W Smith Professor and Chair Department of Otolaryngology— Head and Neck Surgery Columbia University Medical Center and New York Presbyterian Hospital New York, New York, USA Dean M Mancuso AuD Assistant Professor of Audiology Department of Otolaryngology— Head and Neck Surgery Columbia University Medical Center New York, New York, USA Peter L Santa Maria MBBS PhD Instructor Department of Otolaryngology— Head and Neck Surgery Stanford University Stanford, California, USA Adam N Master MD Resident Physician Department of Otolaryngology— Head and Neck Surgery Louisiana State University Health Science Center Shreveport Shreveport, Louisiana, USA Michael J McKenna MD Director Division of Otology and Neurotology Massachusetts Eye and Ear Boston, Massachusetts, USA Sean O McMenomey MD Professor of Otolaryngology and Neurosurgery—Vice Chair Department of Otolaryngology New York University Langone Medical Center New York, New York, USA

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Contributors Cliff A Megerian MD FACS Julius W McCall Professor and Chairman Otolaryngology—Head and Neck Surgery Case Western Reserve University School of Medicine Richard W and Patricia R Pogue Endowed Chair Director Ear, Nose and Throat Institute University Hospitals Case Medical Center Cleveland, Ohio, USA Myles Melton Medical Student Weill Cornell Medical College New York, New York, USA Ted A Meyer MD PhD Associate Professor Department of Otolaryngology— Head and Neck Surgery Medical University of South Carolina Charleston, South Carolina, USA Alan G Micco MD FACS Associate Professor Department of Otolaryngology Northwestern University Feinberg School of Medicine Chicago, Illinois, USA Faith M Mogila ScD Clinical Preceptor Department of Communication Sciences and Disorders Montclair State University Montclair, New Jersey, USA Joseph J Montano EdD Associate Professor of Audiology Department of Otolaryngology Weill Cornell Medical College New York, New York, USA Marc-Elie Nader MD Assistant Professor Department of Otolaryngology University of Montreal Montreal, Quebec, Canada John K Niparko MD Professor and Chair Department of Otolaryngology— Head and Neck Surgery Keck School of Medicine of University of Southern California Los Angeles, California, USA

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John S Oghalai MD Associate Professor Department of Otolaryngology— Head and Neck Surgery Stanford University Stanford, California, USA Steven R Otto Chief Audiologist and Coordinator Auditory Brainstem Implant Program House Clinic Los Angeles, California, USA Lorne S Parnes MD FRCSC Professor Departments of Otolaryngology— Head and Neck Surgery and Clinical Neurological Sciences Western University London, Ontario, Canada Dennis Poe MD PhD Associate Professor in Otolaryngology Boston Children’s Hospital Boston, Massachusetts, USA Alicia M Quesnel MD Instructor Department of Otology and Laryngology Harvard Medical School Attending Surgeon Department of Otolaryngology Massachusetts Eye and Ear Infirmary Boston, Massachusetts, USA Habib Rizk MD Neurotology Fellow Otolaryngology Head and Neck Surgery Medical University of South Carolina Charleston, South Carolina, USA Amy L Rutt DO Assistant Professor Department of Otolaryngology— Head and Neck Surgery Mayo Clinic Rochester, Minnesota, USA Robert T Sataloff MD Professor and Chairman Department of Otolaryngology— Head and Neck Surgery Senior Associate Dean for Clinical Academic Specialties Drexel University College of Medicine Philadelphia, Pennsylvania, USA

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David A Schessel PhD MD Associate Professor Department of Surgery Stony Brook University Stony Brook, New York, USA Marc S Schwartz MD Neurological Surgery House Ear Clinic Los Angeles, California, USA Samuel H Selesnick MD FACS Professor and Vice-Chairman Department of Otolaryngology— Head and Neck Surgery Weill Cornell Medical College New York, New York, USA Maroun T Semaan MD Associate Professor Ear Nose and Throat Institute University Hospitals Case Medical Center Case Western Reserve University Cleveland, Ohio, USA J Caleb Simmons MD Baylor College of Medicine Houston, Texas, USA Eric E Smouha MD Associate Professor Department of Otolaryngology— Head and Neck Surgery Icahn School of Medicine at Mount Sinai New York, New York, USA Jaclyn B Spitzer PhD Professor Department of Otolaryngology— Head and Neck Surgery Columbia University New York, New York, USA Shawn M Stevens MD Resident Surgeon Department of Otolaryngology— Head and Neck Surgery Medical University of South Carolina Charleston, South Carolina, USA Emily Z Stucken MD Michigan Ear Institute Farmington, Hills, Michigan, USA

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Daniel Q Sun MD Radiation Oncology Healthcare Towson, Maryland, USA Maja Svrakic MD Bellevue Hospital—Otolaryngology New York, New York, USA Alex D Sweeney MD Department of Otolaryngology— Head and Neck Surgery Vanderbilt University Nashville, Tennessee, USA Monica Tadros MD FACS Assistant Professor of Otolaryngology— Head and Neck Surgery Director of Facial Plastic and Reconstructive Surgery Columbia University Medical Center New York, New York, USA Elizabeth H Toh MD FACS Department of Otolaryngology— Head and Neck Surgery Lahey Hospital and Medical Center Burlington, Massachusetts, USA

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Andrea Vambutas MD FACS Professor of Otolaryngology and Molecular Medicine Hofstra North Shore— LIJ School of Medicine New Hyde Park, New York, USA

Brent Wilkerson MD Resident Department of Otolaryngology University of California Davis Health System Sacramento, California, USA

Alejandro Vázquez MD Resident Department of Otolaryngology— Head and Neck Surgery Rutgers New Jersey Medical School Newark, New Jersey, USA

Eric P Wilkinson MD Surgeon and Partner, House Clinic Los Angeles, California, USA

Jeffrey T Vrabec MD Professor of Otolaryngology— Head and Neck Surgery Baylor College of Medicine Houston, Texas, USA Cameron C Wick MD Resident Department of Otolaryngology— Head and Neck Surgery Case Western Reserve University School of Medicine Cleveland, Ohio, USA

Robert A Williamson MD Assistant Professor of Otolaryngology— Head and Neck Surgery Baylor College of Medicine Houston, Texas, USA Justin D Wilson AuD Mayo Clinic Health System LaCrosse, Wisconsin, USA Qiu Zhong MD Resident Department of Otolaryngology Northwestern University Feinberg School of Medicine Chicago, Illinois, USA

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Foreword Sataloff’s Comprehensive Textbook of Otolaryngology: Head and Neck Surgery is a component of the most extensive compilation of information in otolaryngology—head and neck surgery to date. The six volumes of the comprehensive textbook are part of a 12-volume, encyclopedic compendium that also includes a six-volume set of detailed, extensively illustrated atlases of otolaryngologic surgical techniques. The vision for the Comprehensive Textbook was realized with the invaluable, expert collaboration of eight world-class volume editors. Chapter authors include many of the most prominent otolaryngologists in the world, and coverage of each subspecialty is extensive, detailed and scholarly. Anil K Lalwani, MD edited the volume on otology/neurotology/skull base surgery. Like all six of the volumes in the Comprehensive Textbook, the otology/neurotology/skull base surgery volume is designed not only as part of the multivolume book, but also to stand alone or in combination with the atlas of otological surgery. Dr Lalwani’s volume covers anatomy and physiology of hearing and balance, temporal bone radiology, medical and surgical treatment of common and rare disorders of the ear and related structures, occupational hearing loss, aural rehabilitation, cochlear and brainstem implantation, disorders of the facial nerve, and other topics. Each chapter is not only replete with the latest scientific information, but also accessible and practical for clinicians. The rhinology/allergy and immunology volume by Marvin P Fried and Abtin Tabaee is the most elegant and inclusive book on the topic to date. Drs Fried and Tabaee start with a history of rhinology beginning in ancient times. The chapters on evolution of the nose and sinuses, embryology, sinonasal anatomy and physiology, and rhinological assessment are exceptional. The volume includes discussions of virtually all sinonasal disorders and allergy, including not only traditional medical and surgical therapy but also complementary and integrative medicine. The information is state-of-the-art. Anthony P Sclafani’s volume on facial plastic and reconstructive surgery is unique in its thoroughness and practicality. The volume covers skin anatomy and physiology, principles of wound healing, physiology of grafts and flaps, lasers in facial plastic surgery, aesthetic analysis of the face and other basic topics. There are extensive discussions on essentially all problems and procedures in facial plastic and reconstructive surgery contributed by many of the most respected experts in the field. The volume includes not only cosmetic and reconstructive surgery, but also information on diagnosis and treatment of facial trauma. The volume on laryngology edited by Dr Michael S Benninger incorporates the most current information on virtually every aspect of laryngology. The authors constitute a who’s who of world experts in voice and swallowing. After extensive and practical discussions of science and genetics, the volume reviews diagnosis and treatment (traditional and complementary) of laryngological disorders. Chapters on laser physics and use, voice therapy, laryngeal dystonia, cough, vocal aging and many other topics provide invaluable “pearls” for clinicians. The volume also includes extensive discussion of surgery for airway disorders, office-based laryngeal surgery, laryngeal transplantation and other topics. For the volume on head and neck surgery, Drs Patrick J Gullane and David P Goldstein have recruited an extra­ ordinary group of contributors who have compiled the latest information on molecular biology of head and neck cancer, principles of radiation, immunobiology, medical oncology, common and rare head and neck malignancies, endocrine neoplasms, lymphoma, deep neck space infections and other maladies. The surgical discussions are thorough and richly illustrated, and they include definitive discussions of free flap surgery, facial transplantation and other subjects. Dr Christopher J Hartnick’s vision for the volume on pediatric otolaryngology was expansive, elegantly scholarly and invaluable clinically. The volume begins with information on embryology, anatomy, genetics, syndromes and other complex topics. Dr Hartnick’s contributors include basic discussions of otolaryngologic examination in a pediatric patient, imaging, hearing screening and aural rehabilitation, and diagnosis and treatment of diseases of the ear, nose, larynx, oral cavity, neck and airway. Congenital, syndromic and acquired disorders are covered in detail, as are special, particularly vexing problems such as chronic cough in pediatric patients, breathing and obstructive sleep apnea in children, pediatric voice disorders, and many other subjects. This volume will be invaluable to any otolaryngologist who treats children.

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All of us who have been involved with the creation of the six-volume Sataloff’s Comprehensive Textbook of Otolaryngology: Head and Neck Surgery and its companion six-volume set of surgical atlases hope and believe that our colleagues will find this new offering to be not only the most extensive and convenient compilation of information in our field, but also the most clinically practical and up-to-date resource in otolaryngology. We are indebted to Mr Jitendar P Vij (Group Chairman) and Mr Ankit Vij (Group President) of M/s Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, India, for their commitment to this project, and for their promise to keep this work available not only online but also in print. We are indebted also to the many otolaryngologists who have contributed to this work not only by editing volumes and writing chapters, but also by asking questions that inspired many of us to seek the answers found on these pages. We also thank especially the great academic otolaryngologists who trained us and inspired us to spend our nights, weekends and vacations writing chapters and books. We hope that our colleagues and their patients find this book useful. Robert T Sataloff MD DMA FACS Professor and Chairman Department of Otolaryngology—Head and Neck Surgery Senior Associate Dean for Clinical Academic Specialties Drexel University College of Medicine Philadelphia, Pennsylvania, USA

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Preface Though a subspecialty within otolaryngology—head and neck surgery, otology/neurotology/skull base surgery is as diverse as the field of medicine itself. And like medicine, it enthralls those who pursue it—whether as a generalist or a specialist. This textbook endeavors to capture the dynamic nature of otology/neurotology/skull base surgery in its pages while providing a broad foundation in its basic and clinical sciences. Written by experts, the chapters encompass the basics such as anatomy and physiology of hearing loss, vestibular dysfunction, facial nerve disorders, and skull base tumors. Radiology has its own chapter, and disease-specific imaging is reviewed in all relevant chapters. Building upon the basics, cutting-edge topics such as cochlear implantation, auditory brainstem implants, and implantable hearing aids are thoroughly covered in their own chapters. Ultimately, this textbook is distinguished by the expertise of its contributors—all leaders in otology/neurotology/skull base surgery. It is the reader who will benefit from absorbing their experience as articulated in this wonderful textbook. Anil K Lalwani MD

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Acknowledgments The editor would like to thank Joseph Rusko, Marco Ulloa, Carol Rogers Field, Bridget Meyer, Thomas Gibbons and the rest of the Jaypee Brothers team. Without their perseverance and hard work, this volume would not have been possible. Special thanks are offered to the authors, who have shared their expertise and experience in order to improve the care of the otology/neurotology/skull base surgery patients. I would also like to thank Mr Jitendar P Vij (Group Chairman), Mr Ankit Vij (Group President), Ms Chetna Malhotra Vohra (Associate Director), Mr Umar Rashid (Development Editor) and Production team of Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, India.

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Contents 1. Anatomy and Physiology of the Auditory System

1

Peter L Santa Maria, John S Oghalai

2. Evaluation of Auditory Function

19

Janet Koehnke, Faith M Mogila, Maris Appelbaum, Joan Besing

3. Middle Ear Mechanics in Normal Hearing, in Diseased Ears, and in Hearing Reconstruction

37

Manohar Bance, Robert A Adamson

4. Anatomy and Physiology of the Vestibular System

57

Daniel Q Sun, Yuri Agrawal

5. Evaluation of Vestibular Disorders

75

Justin D Wilson, Art Ambrosio, Roxanne Cano, Michael E Hoffer

6. Anatomy and Physiology of the Eustachian Tube

83

Ilkka Kivekäs, Dennis Poe

7. Radiology of the Temporal Bone

99

Alexander Filatov, Mari Hagiwara

8. Diseases of the External Ear

119

Myles Melton, Kevin D Brown, Samuel H Selesnick

9. Malignant Tumors of the Temporal Bone

135

Amy L Rutt, Mary J Hawkshaw, Robert T Sataloff

10. Non-Squamous Cell Carcinoma Tumors of the Temporal Bone

149

Maroun T Semaan, Cameron C Wick, Cliff A Megerian

11. Cholesteatoma

179

Eric E Smouha, Emily Stucken, Dennis Bojrab

12. Tympanoplasty and Ossiculoplasty

197

Dennis I Bojrab, Emily Z Stucken, Eric E Smouha

13. Complications of Temporal Bone Infection

219

Daniel Jethanamest, Simon I Angeli

14. Otosclerosis

231

Alicia M Quesnel, Michael J McKenna

15. Tumors of the Middle Ear

243

Alan G Micco, Qiu Zhong

16. Sensorineural Hearing Loss

253

Andrea Vambutas

17. Presbycusis

267

Selena E Heman-Ackah, Steven K Juhn

18. Occupational Hearing Loss

283

Robert T Sataloff

19. Ototoxicity

307

Karen Jo Doyle, Brent Wilkerson

20. Tinnitus

317

Carol Bauer

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21. Meniere’s Disease

331

Daniel H Coelho, Richard A Goldman

22. Temporal Bone Trauma

345

J Caleb Simmons, Alex D Sweeney, Marc-Elie Nader, Robert A Williamson

23. Vestibular Schwannoma

361

Sean McMenomey, Maja Svrakic

24. Meningioma and Other Non-vestibular Schwannoma Tumors of the CPA

419

Adam A Master, Maura K Cosetti

25. Jugular Bulb and Jugular Foramen in Ear Diseases

435

C Eduardo Corrales, John S Oghalai

26. Encephalocele and CSF Leak

459

Shawn M Stevens, Habib Rizk, Ryan A Crane, Ted A Meyer

27. Presbystasis and Balance in the Elderly

477

David A Schessel

28. Inner Ear Dehiscence

491

Jason A Beyea, Lorne S Parnes, Sumit K Agrawal

29. Peripheral Vertigo

505

Jeffrey T Vrabec, Marc-Elie Nader

30. Central Vertigo

517

Robert W Eppsteiner, Deema Fattal, Marlan R Hansen

31. Aural Rehabilitation and Hearing Aids

529

Jaclyn B Spitzer, Dean M Mancuso, Joseph J Montano

32. Implantable Middle Ear and Bone Conduction Devices

545

Alejandro Vázquez, Robert W Jyung

33. Cochlear Implants

557

Maura K Cosetti, Divya Chari, Anil K Lalwani

34. Auditory Brainstem Implants

573

Eric P Wilkinson, Steven R Otto, Marc S Schwartz, Derald E Brackmann

35. Inner Ear Molecular Therapies

581

Manohar Bance, Anil K Lalwani

36. Anatomy and Physiology of the Facial Nerve

617

Ruwan Kiringoda, John K Niparko, Lawrence R Lustig

37. Facial Nerve Testing

627

Sachin Gupta, Brandon Isaacson

38. Facial Nerve Paralysis

635

Elizabeth H Toh

39. Facial Nerve Tumors

649

Gregory J Basura, H Alexander Arts

40. Facial Nerve Reanimation

663

Monica Tadros

Index

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1

Otology/Neurotology/Skull Base Surgery

CHAPTER

Anatomy and Physiology of the Auditory System

1

Peter L Santa Maria, John S Oghalai

PINNA (AURICLE) The pinna is composed of fibroelastic cartilage covered by skin. This cartilage is continuous with that of the external audi­ tory canal (EAC). Anteriorly the cartilage is adherent to the skin, but posteriorly there is a loose areolar layer in between. The dimensions of characteristics of the pinna include (Fig. 1.1)1,2 a height of 5–6 cm, width 55% of height, forms an angle that is 20° from the vertical plane, has an auricle that diverges from the occipital scalp at 21°–30°, forms an angle of 10 ms. It is most efficient at 2 kHz. It provides rigi­ dity and blood supply to the ossicular chain and reduces physiological noise from chewing and talking. The stapedial reflex39 is the contraction of the stapedial muscle that occurs bilaterally to sound presented to one ear. The stapedial reflex is a measure of the integrity of the inner hair cells (IHCs). Contraction of the stapedial muscle occurs at approximately 70–100 (mean 85) dBHL above threshold. The ipsilateral reflex occurs at approximately 2–14 dB less than the contralateral ear. Stimulating both ears lowers the threshold by 3 dB. If a patient has hearing loss combined with the reflex threshold greater than the limits of the audiometer (approximately 120 dB), the reflex will be absent. It is also absent in 5–20% of normal people (Fig. 1.11). The tympanic diaphragm is a series of mucosal folds that separate the epitympanum from the mesotympanum and the mastoid. Its components are the malleus head, body of incus, lateral incudal fold, medial incudal fold, anterior malleolar fold, lateral malleolar fold, and tensor tympani fold.40 There are two narrow passages that breach the diaphragm, the anterior and posterior tympanic isth­ muses. The anterior tympanic isthmus is medial to the body of the incus, passing between the stapes, long pro­ cess incus, and the tensor tympani tendon. The posterior tympanic isthmus is between the pyramidal process, short process of incus and posterior incudal ligament, medial incudal fold, stapes and stapedial tendon (Fig. 1.12).

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Otology/Neurotology/Skull Base Surgery

Fig. 1.12: The tympanic diaphragm and connections between the epitympanun and the mesotympanum. Areas of communication are highlighted. Source: Adapted from Proctor.40

Clinical comment •• The tympanic diaphragm provides some resistance to the spread of cholesteatoma between the mesotym­ panum and epitympanum. The patency of the tym­ panic isthmus and aditus ad antrum are important for aeration of the mastoid. In surgery for chronic otitis media, sometimes the head of the malleus and the body of the incus are removed with the attaching folds and ligaments to increase aeration between the middle ear and mastoid. Beneath the floor of the attic and in the upper meso­ tympanum there are three compartments.40 The inferior incudal space is from the inferior surface of the incus later­ ally to the posterior malleolar fold limited medially by the medial incudal fold and anteriorly by the interossicular fold. The posterior pouch of von Troeltsch is between the TM and the posterior malleolar fold. Its inferior edge often contains the chorda tympani. It opens inferiorly toward the posterior mesotympanum. The anterior pouch of von Troe­ ltsch is between the TM and the anterior malleolar fold. The chorda tympani18,26 runs in the mesotympanum and supplies taste to the anterior two-thirds of the tongue and is secretomotor to the submandibular and sublingual glands. The taste cell bodies lie in the geniculate ganglion. It leaves the facial nerve, on average, 5 mm (a range of -1 to 11 mm) above the stylomastoid foramen and runs in the canaliculus of chorda tympani. It enters the middle ear via the ita chordae posterius (in the posterior lateral wall of the middle ear) with the posterior tympanic artery.

It lies between the pyramidal eminence and the tympanic annulus. It runs through the middle ear lateral to the long process of the incus and the tendon of tensor tympani but medial to the neck of the malleus and posterior malleolar ligament. It exits the middle ear at the iter chordae anterius to run in the canal of Huguier. The chorda tympani may have a number of variations. In the middle ear it may pass lateral to the TM or may pass lateral to the malleus. In the mastoid it may arise distal to the stylomastoid foramen or may arise as high as the lateral semicircular canal. The tympanic plexus42 lies on the cochlea promontory. The incoming fibers include parasympathetics that come from Jacobson’s nerve (CN IX) and Arnold’s nerve (CN X) and sympathetic branches from the internal carotid artery Its outgoing fibers include the lesser superficial petrosal nerve that carry parasympathetic branches of CN IX. It leaves in a small canal beneath the tensor tympani. It is joined by parasympathetic branches of CN VII and eme­rges lateral to the greater superficial petrosal nerve in the middle fossa before leaving by the foramen ovale. The plexus also has a branch to the greater superficial petrosal nerve and TM mucosal branches. Clinical comment •• A tympanic neurectomy is a potential treatment for Frey’s syndrome after parotidectomy by interrupting the misdirected parasympathetic supply via the lesser superficial petrosal nerve.43,44 The hypotympanum lies beneath the floor of the bony EAC and contains hypotympanic air cells with the jugular bulb posterior inferiorly and the internal carotid artery anterior inferiorly. Either may be dehiscent in the hypotympanum. The blood supply of the middle ear45 is by branches of the external carotid, internal carotid, and basilar arteries. The branches of the external carotid artery branches include the anterior tympanic artery that runs from the inter­nal maxillary artery through the petrotympanic fis­ sure. It has a superior branch that supplies the anterior lateral epitympanum, a posterior branch that supplies the TM, incudostapedial joint and lateral tegmen, and an ossi­ cular branch. The ossicular branch further divides into a mallear and incudal branch. The external carotid also gives the deep auricular artery via the maxillary internal maxil­ lary artery through the inferior bony EAC. It has an ante­ rior and posterior branch. The inferior tympanic artery runs from the ascending pharyngeal artery through the inferior tympanic canaliculus. The stylomastoid artery runs

Chapter 1: Anatomy and Physiology of the Auditory System from the postauricular artery running up through the stylo­ mastoid foramen. The stylomastoid artery also provides the posterior tympanic artery. There is a mastoid branch from the occipital artery. A tubal branch comes from the accessory meningeal artery. The superficial petrosal artery branches from the middle meningeal artery and runs with the greater superficial petrosal nerve. A superior tympanic artery branches from the middle meningeal artery through the superior tympanic canaliculus with the lesser super­ ficial petrosal nerve. The internal carotid artery supplies blood to the middle ear via its caroticotympanic branches2 that come direct from the internal carotid artery. The basi­ lar artery supplies the middle ear via branches of the sub­ arcuate artery, itself coming from the labyrinthine artery, or the anterior inferior cerebellar artery.

9

Fig. 1.13: A coronal view of the boundaries of Prussak’s space.

Clinical comment •• A persistent stapedial artery is the persistence of the artery to the second brachial arch. It runs from the internal carotid artery over the promontory, through the stapes arch and enters the fallopian canal above the oval window. It then runs with the facial nerve up­ ward to supply a region of dura. Its ligation may com­ prise cerebral function and therefore is a potential hazard during stapedectomy.46 The inferior tympanic artery is the usual blood supply to a glomus tympanicum tumor.47 The middle ear and Eustachian tube forms from the expansion of the first pouch. The epitympanum and antrum are developed by birth. The expansion of the first pouch leads to the development of four primary sacs.40 The saccus medius forms the epitympanum and divides into three smaller spaces, the medial (to later form Prussak’s space), the posterior, and the anterior. The saccus anti­ cus forms the anterior pouch of von Troeltsch. The saccus superior forms the posterior pouch of von Troeltsch. The saccus posticus forms the posterior middle ear and hypo­ tympanum (Fig. 1.13). Clinical comment •• Knowledge of the folds and spaces in the middle ear helps with the understanding of the routes of spread of cholesteatoma.48 The main routes of spread for choles­ teatoma in decreasing order are via the poste­ rior epitympanum, posterior mesotympanum, and ante­ rior tympanum. From the posterior epitympanum, it can penetrate the superior incudal space (running

lateral to the body of the incus), then to the antrum and then the mastoid. It may also go through the floor of Prussak’s space to the posterior pouch of von Troeltsch (running between the TM and posterior malleolar fold) to the posterior mesotympanum then to the stapes, round window, sinus tympani, and facial recess. The posterior mesotympanum route forms as retraction forms a sac medial to the neck of the mal­leus and incus then to the sinus tympani and facial recess. The anterior epitympanum route forms by retraction anterior to the malleus head, then to the anterior pouch of von Troeltsch (between the TM and the anterior malleolar fold), then to the supratubal recess. This route often causes early facial nerve palsy. •• Acquired cholesteatoma is seen as squamous epithe­ lium extending into Prussak’s space. The boundaries of Prussak’s space are the pars flaccida (laterally), the neck of the malleus (medially), the lateral process of the malleus (inferiorly), and the lateral malleolar fold (superiorly).49 •• Meningitis may result from the spread of infection between the middle ear and the cerebrospinal fluid (CSF) via a number of anatomical and pathological routes. These potential connections are from the mid­ dle ear to the inner ear, from the middle ear directly to the CSF and from the inner ear to the CSF. The oval window connects the middle ear to the inner ear and is the most common route of spread. The middle ear may connect to the CSF via Hyrtl’s fissure, a congenital cleft between the hypotympanum and the posterior

10

Otology/Neurotology/Skull Base Surgery fossa, or the petrosquamous sinus (of Lushka) which is an occasional embryological remnant often open in infancy. It usually connects the middle ear and the transverse or sigmoid sinus (although it is highly vari­ able). Retrograde spread from the middle ear can also occur via the internal auditory vein or the mastoid emissary vein. Infection can spread from the inner ear to the cerebrospinal fluid directly through the internal auditory canal (IAC) fundus, via modiolar end defects or via the cochlear aqueduct.

The resonant frequencies of the external and middle ears are determined by their design.50 This results in a combined external ear gain of 15–20 dB over 2–7 kHz and 5 dB at 3 kHz in the middle ear. The resonance of the middle ear is includes the air space contained within the mastoid antrum. This effect is lost by blocking the antrum, as is sometimes performed in chronic ear surgery. The combined resonance of the external and middle ear is thought to produce the typical notch in the audiogram seen in sensory hearing loss associated with noise induced hearing loss. The gain provided via the various parts of the ear include51 the concha with a 10 dB gain at 5 kHz and the EAC with a 10 dB gain at 2–5 kHz. In infants the EAC provides a 15 dB gain at 3 kHz (at approximately 8 kHz in infants) and reaches adult value after age two and a half. The middle ear52 has a gain of 5 dB at 3 kHz and the TM has a gain at 800–1600 Hz. Sound is transferred from the TM to the cochlear with a gain according to the transformer ratio theory.53,54 It accounts for a total gain of approximately 25–30 dB. In normal subjects up to 25 dB variations in middle ear mechanics can occur. At 1 kHz, the ratio of gain from the TM to the cochlear is 82.5. This is a combination of three levers: the hydraulic, ossicular, and catenary. The hydraulic lever provides a gain of 17–20 times relates to the ratio of the area of the oval window to the TM. The ossicular lever has a gain of 1.3 represents the ratio of the long axis of the malleus to the long process of the incus. The catenary lever provides a gain of 2 due to the outward convexity of TM with its radial arrangement of collagen fibers. The levers have greatest efficiency at 1 kHz. Frequen­ cies > 1 kHz lead to a reduction in the efficiency of the levers. Above 1 kHz, the hydraulic lever changes as vibra­ tions are broken up into smaller vibratory patterns, while the ossicular lever provides more slippage in the axis of rotation of the ossicles. The TM has its greatest movement at its inferior edge at 2 kHz. Above 6 kHz vibrations are broken up into small zones. The annular ligament provides

approximately 90% of the stiffness. No movement occurs at the malleoincudal joint at physiological sound pressures. Clinical comment •• Sound is localized to the worse-hearing ear in a con­ ductive hearing loss with the Weber test. One expla­ nation of this in ossicular fixation is that increased ossicular chain stiffness leads to less shunting of pres­ sure out of the cochlea, which increases bone vibra­ tion detection.55

INNER EAR The cochlea is 5 mm in height. The cochlea duct is 34 mm and has two and three quarter turns around the helicot­ rema. The modiolus points laterally, anteriorly, and inferi­ orly. It has a similar orientation as the EAC.56 The cochlea aqueduct transmits the periotic duct (perilymphatic duct) between the basal turn of the scala tympani to the media of the jugular fossa (Table 1.1 and Fig. 1.14).21 Clinical comment •• The cochlea aqueduct is a potential route of spread of meningitis. Its dissection during a translabyrinthine procedure releases cerebral spinal fluid pressure. During this procedure, it marks the inferior limit of dissection as further inferior dissection puts CN IX–XI at risk. 57 Hair cells62,63 do not possess true stereocilia, which require a nine plus two arrangement of microtubules and do not have kinocilia. They are like microvilli with an actin core. They increase in length along the cochlea duct. The first-order neurons of the cochlea nerve lie in the spiral ligament, compared to within the IAC for the vestibular nerve. The IHCs are arranged to form a single row of hair cells and are flask shaped. They have only afferent synapses. Their stereocilia do not attach into the tectorial membrane, they are deflected by fluid in between tectorial membrane and reticular lamina. Cilia deflection causes mechanically gated ion channels to open allowing potassium and calcium to enter the cell. This then causes voltage gated calcium channels to open, causing depolarization. Outer hair cells (OHCs)64,65 are arranged in three rows and are cylinder shaped. They have both afferent and efferent synapses. They are unique to mammals. Their stereocilia attach into the bottom surface of the tectorial membrane. They are responsible for the sensitivity of hearing and provide the “cochlea amplifier”. They do this by sensing the incoming sound wave, and then generating force in synchrony with

Chapter 1: Anatomy and Physiology of the Auditory System

11

Table 1.1 Functions of the parts within the cochlea

Part

Composition

Function

Stria vascularis

Three epithelial layers (marginal, intermedi­ ate, basal), blood vessels, pericytes, melano­ cytes, endothelial cells

Produces endolymph Source of endocochlear potential Primary producer of energy for the cochlea

Spiral ligament

Mainly type I collagen Contains five types of aquaporins

Role in endocochlear potential Fluid homeostasis

Spiral prominence cells

Express pendrin and aquaporins

Ion + fluid regulation

Spiral limbus + Huschke’s teeth cells

Ion + fluid regulation Tectorial membrane maintenance (glycosaminoglycans, tectorins) Potassium recycling from IHCs

Pillar cells Inner/outer

Maintain spatial relationships between hair cells

Dieter’s cells (between the OHCs)

Mechanical support of organ of Corti

Hensen

Potassium recycling

Bottchers (Not in apical turn)

Secretory HCO3 regulation

Claudius

Potassium recycling

Spaces of Nuel

Contain perilymph

Basilar membrane

Inner/zona arcuata (under tunnel of Corti), thin Outer/zona pectinata Thick, striated Covered by vascular layer beneath Permits nearly unimpeded passage to organ of Corti (therefore fluid resembles perilymph)

Frequency tuning

Reissner’s membrane

Possible area of fluid transport between scala

Tectorial membrane

Coupling of vibrations to OHC stereocilia

(IHCs, inner hair cells; OHCs, outer hair cells).

it to increase the vibration of the basilar membrane. This provides a gain of up to 60 dB. The plasma membrane of the OHC contains prestin, which is a motor protein that senses the voltage within the cell and generates force. This causes the length of the OHC to elongate and contract, a phenomenon called electromotility. By adding this addi­ tional energy to the cochlear traveling wave, viscous dam­ ping forces within the cochlea are overcome, leading to high-frequency hearing.

Clinical comment •• OHCs are the most susceptible of the hair cells to ototoxicity. OHCs are also typically lost after loud noise exposure and with aging. Loss of OHCs leads to hearing loss and decreased word recognition ability. Recruitment is the perception of exaggerated sound and reduced dynamic range that also occurs when OHCs are lost.

Clinical comment •• Otoacoustic emissions (OAEs) are a measure of OHC function. They are absent if hearing loss is > 50 dBHL. There are various types of OAEs that can be measured, including spontaneous, transient evoked, stimulus frequency evoked, and distortion product evoked.64,66 OAEs are the most common type of test used to screen for hearing loss in newborn babies.

The basilar membrane has a tonotopic organization. This is primarily because its stiffness decreases from base to apex, although its width (and hence its mass) also increases along the length of the cochlea. The traveling wave of the basilar membrane vibrates with maximum amplitude at a place along the cochlea that is dependent on the frequency of the sound presented. The corresponding hair cells stimulate the adjacent nerve fibers, which are organized according to the frequency at which they are

12

Otology/Neurotology/Skull Base Surgery Table 1.2: The fluid composition in the cochlea

Fluid

Like

K+

Na+

Endo­ lymph

Intracel­ lular

High (144 mM)

Low (5 mM)

Perilymph

Extracel­ lular, CSF

Low (10 mM)

High (140 mM)

Other

Contains β2 transferrin

(CSF, cerebrospinal fluid).

Fig. 1.14: A cross section of the cochlea.58–61

most sensitive. The lower frequencies travel further (to the apex). The basilar membrane response allows complex sounds to be broken up into narrow bands of frequencies. The cochlea fluids67,68 are predominantly composed of potassium (K+) and sodium (Na+). The difference in potassium concentrations between the compartments leads to an endocochlear potential of +80–100 mV. This is maintained by a Na+/K+ ATPase within the stria vascularis (Table 1.2). Clinical comment •• β2 transferrin can be used to identify a cerebrospinal fluid or perilymphatic fluid leak. The arterial supply45,69,70 (Fig. 1.15) of the inner ear is via branches of the labyrinthine artery (a branch of the anterior inferior cerebellar artery, but sometimes comes from the basilar or superior cerebellar artery). It runs in the IAC before becoming the anterior vestibular artery. This will supply the utricle, superior semicircular canal, and lateral semicircular canal (the embryological pars superior)). From this, the common cochlear artery branches. This branches again into two further arteries, the main cochlear artery and the vestibulocochlear artery. The main cochlear artery supplies the apical three quarters of the cochlea and the modiolus. It gives the

Fig. 1.15: The tonotopical arrangement of the cochlea.

external radiating arterioles, which gives four networks supplying the cochlea. The spiral ligament branches give branches to the scala vestibule and the scala tympani. The other networks are to the stria vascularis and the spiral prominence. The main cochlea artery also gives the internal radiating arterioles that provide the limbus vessels and marginal vessels. The vestibulocochlear artery gives the posterior vestibular artery that supplies the saccule and posterior semicircular canal (the embryological pars inferior). It also gives the cochlear ramus artery to supply the basal one quarter of the cochlea. The venous drainage of the inner ear (Fig. 1.16) is simi­ larly matched to the arterial supply. The anterior spiral vein, draining the spiral ligament and scala vestibule, and the posterior spiral vein, draining the scala media and scala tympani, both drain into the common modiolar vein. The anterior vestibular vein, draining the pars superior, the posterior vestibular vein, draining the pars inferior, and the vein of the round window all drain into the vesti­ bulocochlear vein. The common modiolar vein joins the vestibulocochlear vein to form the inferior cochlear vein,

Chapter 1: Anatomy and Physiology of the Auditory System

Fig. 1.16: The arterial supply of the cochlea.72

which then drains to the inferior petrosal vein via the canal of Cotugno. The membranous semicircular canals drain into the vein of the vestibular aqueduct that then joins the sigmoid sinus. Sometimes there is also an internal audi­ tory vein that flows into the inferior petrosal sinus via the IAC (Fig. 1.17). Cochlear neurons can be divided into type I or type II.72 Afferent nerve fibers are unmyelinated and run from the organ of Corti, through the habenula perforata, to the spiral ganglion. Spiral ganglion neurons are bipolar and acquire the myelin in the modiolus. This can be compared to the vestibular neurons that are myelinated and gain their myelin sheath as they cross the basement membrane dire­ctly under the sensory epithelium. 95% of the affer­ ent nerve fibers synapse with IHCs. These are called type I afferent neurons, and are the primary source of auditory input to the brain. Type II afferent neurons receive input from OHCs, and their purpose is unknown. Efferent fibers are the terminations of descending olivocochlear nerve fibers (Rasmussen’s bundle). They come from the brainstem and synapse onto the OHCs. Their function is unknown at this time, but they may be important to under­ standing speech in noisy background environments. The sensory epithelium in the inner can be divided according to embryological origin into the pars superior (supplying the superior semicircular canal, lateral semicircular canal and utricle) and pars inferior (supplying the posterior semi­ circular canal and saccule) (Table 1.3). The endolymphatic fluid73 is produced predominantly by the stria vascularis but also by the planum semilunatum (around cristae), the dark vestibular cells and from the perilymph across the labyrinth membranes. Vasopressin plays a role in its formation. It moves by longitudinal flow

13

Fig. 1.17: The venous drainage of the cochlea.72

Table 1.3: A comparison of cochlear neurons

Type

I

II

Incidence

95%

5%

Hair cell supply

IHC

OHC

Number of neurons per row

1

3–5

Ratio of neuron to hair cell

10:1

1:10

Size

Large

Small

Myelination

Yes (acquire in the modiolus)

No

(IHCs, inner hair cells; OHCs, outer hair cells).

and radial exchange. Longitudinal flow is slow at 0.004– 0.007 mm/min and flows from the stria vascularis to the scala media to the ductus reunions to the saccule and them to the endolymphatic sac. Radial exchange is rapid and occurs via an exchange and balance of chemicals.

INTERNAL AUDITORY CANAL The IAC has a diameter of 4.5 mm with a 2 mm difference in an individual between sides, it is suggestive of a pathological condition (such as a vesti­ bular schwannoma). Its length along the posterior wall measures 8 mm with 1 mm. It is usually patent, but neither transmits pressure or allows free spinal fluid to flow. Membranous abnor­ malities can either be incomplete or complete. Scheibe is an incomplete type, cochleosaccular dysplasia (of the pars inferior) with a malformed membranous canal. The organ of Corti is partially or totally missing with a normal bony canal. Alexander is also an incomplete type and is partial (localized to the basal turn) aplasia of cochlea duct occurring with high-frequency sensory hearing loss. Bing Siebemann malformations involve complete membranous dysplasia and are associated with Jervell and Lange-Nielsen syndrome and Usher’s syndrome (Table 1.5 and Fig. 1.22).

Fig. 1.21: The embryological development of the otocyst. Table 1.5: Classification of inner ear malformations84,85

Arrested development

Features

3rd week (early)

Michel’s deformity (complete labyrinthine aplasia, i.e. no inner ear)

3rd week (late) Cochlea aplasia (absent cochlea, deformed vestibule)

8

4th week

Common cavity (same chamber)

11

5th week

Cochlear agenesis (incomplete partition type I, labyrinth is cystic but separate) Normal vestibular aqueduct

6th week

Cochlear hypoplasia (≤1 turn of cochlea, hypoplastic labyrinth)

7th week

Incomplete partition (Mondini’s) 1½ turns (cystic appearance of cochlea apex only)

8th week

Normal

Dorsal pouch of otocyst

Endolymphatic duct

11



Utricle and semicircular ducts

11

Semicircular canals

19–22

Labyrinthine ossification

23

Total development

26

16

Otology/Neurotology/Skull Base Surgery

Fig. 1.23: The central auditory pathway. Source: Redrawn from Nieuwenhuys.87

Fig. 1.22: A classification of inner ear malformations. Source: Redrawn from Jackler et al.84

AUDITORY CORTEX The auditory cortex is in the lateral (Sylvian) fissure.84 It is arranged with low frequencies superior and high fre­ quencies inferior. The auditory cortex exhibits plasticity in that it has the ability to modify or reorganize. Although this plasticity occurs throughout life, it occurs to a greater extent at younger ages. Modification of the tonotopic orga­nization of the auditory cortex occurs after hearing loss and with rehabilitation of hearing (Fig. 1.23). Clinical comment •• The auditory brainstem response is a test of the audi­ tory pathway85,86 Electrodes are placed at the mastoid and record the response to broadband clicks (cen­ tered on 3 kHz) or frequency specific tone bursts played by ear phones. It is absent when the pure tone

average is >65 dB or age greater than approximately 65. Typically, five to seven peaks occur within 10 ms. The waves correspond to the following areas of the auditory pathway: Wave I—distal eighth nerve, cor­ responds with the action potential in electrocochleo­ graphy, Wave II—proximal VIII/cochlear nuclei (dorsal + ventral), Wave III—superior olivary nucleus, Wave IV—lateral lemniscus, Wave V—contralateral inferior colliculus, Wave VI—Medial geniculate nucleus, Wave VII—Auditory cortex. Note: Most fibers cross midline at superior olivary nucleus, while some continue uncrossed to inferior colliculus.88-90

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Chapter 1: Anatomy and Physiology of the Auditory System 7. Song R, Song Y, Qi K, et al. The superior auricular artery and retroauricular arterial island flaps. Plast Reconstr Surg. 1996;98(4):657-67; discussion 68-70. 8. Wright CG. Development of the human external ear. J Am Acad Audiol. 1997;8(6):379-82. 9. Klockars T, Rautio J. Embryology and epidemiology of microtia. Facial Plast Surg. 2009;25(3):145-8. Epub 2009/ 10/08. 10. Whitfield IC. Mechanisms of sound localization. Nature. 1971;233(5315):95-7. Epub 1971/09/10. *11. Kelly KE, Mohs DC. The external auditory canal. Anatomy and physiology. Otolaryngol Clin North Am. 1996;29(5): 725-39. 12. Chandler JR. Malignant external otitis and osteomyelitis of the base of the skull. Am J Otol. 1989;10(2):108-10. 13. Alberti PW. Epithelial migration on the tympanic mem­ brane. J Laryngol Otol. 1964;78:808-30. 14. Santa Maria PL, Redmond SL, McInnes RL, et al. Tympa­ nic membrane wound healing in rats assessed by trans­ criptome profiling. Laryngoscope. 2011;121(10):2199-213. doi: 10.1002/lary.22150. 15. Santa Maria PL, Redmond SL, Atlas MD, et al. Histology of the healing tympanic membrane following perforation in rats. Laryngoscope. 2010;120(10):2061-70. 16. Applebaum EL, Deutsch EC. Fluorescein angiography of the tympanic membrane. Laryngoscope. 1985;95(9 Pt 1): 1054-8. 17. Mehta RP, Rosowski JJ, Voss SE, et al. Determinants of hearing loss in perforations of the tympanic membrane. Otol Neurotol. 2006;27(2):136-43. 18. Gray O. The chorda tympani. J Laryngol Otol. 1953;67(3): 128-38. 19. Proctor B, Nielsen E, Proctor C. Petrosquamosal suture and lamina. Otolaryngol Head Neck Surg. 1981;89(3 Pt 1): 482-95.. 20. Bellucci RJ, Fisher EG, Rhodin J. Ultrastructure of the round window membrane. Laryngoscope. 1972;82(6):1021-6. 21. Su WY, Marion MS, Hinojosa R, et al. Anatomical mea­ surements of the cochlear aqueduct, round window mem­ brane, round window niche, and facial recess. Laryngo­ scope. 1982;92(5):483-6. 22. Stewart TJ, Belal A. Surgical anatomy and pathology of the round window. Clin Otolaryngol Allied Sci. 1981;6(1): 45-62. 23. Monkhouse WS. The anatomy of the facial nerve. Ear Nose Throat J. 1990;69(10):677-83, 86-7. 24. Proctor B, Nager GT. The facial canal: normal anatomy, variations and anomalies. I. Normal anatomy of the facial canal. Ann Otol Rhinol Laryngol Suppl. 1982;97:33-44. 25. Sando I, English GM, Hemenway WG. Congenital anomalies of the facial nerve and stapes: a human temporal bone report. Laryngoscope. 1968;78(3):316-23. 26. Nager GT, Proctor B. The facial canal: normal anatomy, variations and anomalies. II. Anatomical variations and anomalies involving the facial canal. Ann Otol Rhinol Laryngol Suppl. 1982;97:45-61. *27. Proctor B. The anatomy of the facial nerve. Otolaryngol Clin North Am. 1991;24(3):479-504. *References with asterisks refer to critical sources.

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28. Proctor B. Surgical anatomy of the posterior tympanum. Ann Otol Rhinol Laryngol. 1969;78(5):1026-40. 29. Donaldson JA, Anson BJ, Warpeha RL, et al. The surgical anatomy of the sinus tympani. Arch Otolaryngol. 1970;91 (3):219-27. 30. Petrus LV, Lo WW. The anterior epitympanic recess: CT anatomy and pathology. AJNR Am J Neuroradiol. 1997;18 (6):1109-14. 31. Gluth MB, Cohen MA, Friedland PL, et al. Surgical anatomy of the anterior supralabyrinthine air cell tract. J Laryngol Otol. 2011;125(10):1009-13. Epub 2011/06/15. 32. Richany SF, Anson BJ, Bast TH. The development and adult structure of the malleus, incus and stapes. Q Bull Northwest Univ Med Sch. 1954;28(1):17-45. 33. Anson BJ, Donaldson JA, Warpeha RL, et al. The surgical anatomy of the ossicular muscles and the facial nerve. Laryngoscope. 1967;77(8):1269-94. 34. Todd NW, Creighton FX Jr. Malleus and incus: correlates of size. Ann Otol Rhinol Laryngol. 2013;122(1):60-5. 35. Anson BJ, Bast TH. Anatomical structure of the stapes and the relation of the stapedial footplate to vital parts of the otic labyrinth. Ann Otol Rhinol Laryngol. 1958;67(2):389-99. 36. Backous DD, Minor LB, Aboujaoude ES, et al. Relationship of the utriculus and sacculus to the stapes footplate: anato­ mic implications for sound-and/or pressure-induced otolith activation. Ann Otol Rhinol Laryngol. 1999;108(6):548-53. 37. Margolis RH, Levine SC. Acoustic reflex measures in audio­ logic evaluation. Otolaryngol Clin North Am. 1991;24(2): 329-47. 38. Borg E, Counter SA. The middle-ear muscles. Sci Am. 1989; 261(2):74-80. 39. Hall CM. Stapedial reflex decay in retrocochlear and cochlear lesions. Review of procedures and methods for conducting SRD tests. Ann Otol Rhinol Laryngol. 1977;86 (2 pt. 1):219-22. *40. Proctor B. The development of the middle ear spaces and their surgical significance. J Laryngol Otol. 1964;78:631-48. 41. McMinn RMH, Last RJ. Last’s anatomy: regional and applied, 9th edn. Edinburgh: Elsevier Health Sciences; 1994. 705p. 42. Tekdemir I, Aslan A, Tuccar E, et al. An anatomical study of the tympanic branch of the glossopharyngeal nerve (nerve of Jacobson). Ann Anat. 1998;180(4):349-52. 43. Daud AS, Pahor AL. Tympanic neurectomy in the manage­ ment of parotid sialectasis. J Laryngol Otol. 1995;109(12): 1155-8. 44. Thomas RL. Tympanic neurectomy and chorda tympani section. Aust N Z J Surg. 1980;50(4):352-5. Epub 1980/08/01. 45. Janfaza P, Nadol JB Jr, Galla RJ, et al. Surgical anatomy of the head and neck. Cambridge, MA: Harvard University Press; 2011. 932 p. 46. Pahor AL, Hussain SS. Persistent stapedial artery. J Laryngol Otol. 1992;106(3):254-7. Epub 1992/03/01. 47. Hesselink JR, Davis KR, Taveras JM. Selective arteriogra­ phy of glomus tympanicum and jugulare tumors: tech­ niques, normal and pathologic arterial anatomy. AJNR Am J Neuroradiol. 1981;2(4):289-97. *48. Jackler RK. The surgical anatomy of cholesteatoma. Oto­ laryngol Clin North Am. 1989;22(5):883-96.

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49. Palva T, Northrop C, Ramsay H. Aeration and drainage pathways of Prussak’s space. Int J Pediatr Otorhinolaryngol. 2001;57(1):55-65. Epub 2001/02/13. 50. Huttenbrink KB. The mechanics of the middle-ear at static air pressures: the role of the ossicular joints, the function of the middle-ear muscles and the behaviour of stapedial prostheses. Acta Otolaryngol Suppl. 1988;451:1-35. 51. Caiazzo AJ, Tonndorf J. Ear canal resonance and temporary threshold shift. Otolaryngology. 1978;86(5):ORL-820. 52. Garcia-Gonzalez A, Gonzalez-Herrera A. Effect of the middle ear cavity on the response of the human auditory system. J Acoust Soc Am. 2013;133(5):3544. 53. Koike T, Wada H, Kobayashi T. Modeling of the human middle ear using the finite-element method. J Acoust Soc Am. 2002;111(3):1306-17. 54. Gan RZ, Reeves BP, Wang X. Modeling of sound transmis­ sion from ear canal to cochlea. Ann Biomed Eng. 2007;35 (12):2180-95. 55. Sichel JY, Freeman S, Sohmer H. Lateralization during the Weber test: animal experiments. Laryngoscope. 2002; 112(3):542-6. 56. Toth M, Alpar A, Bodon G, et al. Surgical anatomy of the cochlea for cochlear implantation. Ann Anat. 2006;188(4): 363-70. 57. Gopen Q, Rosowski JJ, Merchant SN. Anatomy of the normal human cochlear aqueduct with functional implications. Hear Res. 1997;107(1-2):9-22. 58. Kimura RS. The ultrastructure of the organ of Corti. Int Rev Cytol. 1975;42:173-222. 59. Lim DJ. Cochlear anatomy related to cochlear microme­ chanics: A review. J Acoust Soc Am. 1980;67(5):1686-95. *60. Lim DJ. Functional structure of the organ of Corti: a review. Hear Res. 1986;22:117-46. 61. Harada Y, Tagashira N, Takunida M, et al. Three-dimensional ultrastructure of cochlea: a review. Adv Otorhinolaryngol. 1990;45:49-68. 62. Roberts WM, Howard J, Hudspeth AJ. Hair cells: transduc­ tion, tuning, and transmission in the inner ear. Ann Rev Cell Biol. 1988;4:63-92. 63. Meyer AC, Moser T. Structure and function of cochlear afferent innervation. Curr Opin Otolaryngol Head Neck Surg. 2010;18(5):441-6. 64. Brownell WE. Outer hair cell electromotility and otoacous­ tic emissions. Ear Hear. 1990;11(2):82-92. 65. Dallos P. The role of outer hair cells in cochlear function. Prog Clin Biol Res. 1985;176:207-30. 66. Shulman A, Goldstein B, Strashun AM. Final common pathway for tinnitus: theoretical and clinical implications of neuroanatomical substrates. Int Tinnitus J. 2009;15(1): 5-50. Epub 2009/10/22. 67. Zorowka PG. Otoacoustic emissions: a new method to diagnose hearing impairment in children. Eur J Pediatr. 1993;152(8):626-34. 68. Guinan JJ, Jr, Salt A, Cheatham MA. Progress in cochlear physiology after Bekesy. Hear Res. 2012;293(1-2):12-20. 69. Schratzenstaller B, Janssen T, Alexiou C, et al. Confirmation of G. von Bekesy’s theory of paradoxical wave propagation along the cochlear partition by means of bone-conducted auditory brainstem responses. ORL J Otorhinolaryngol Relat Spec. 2000;62(1):1-8. *References with asterisks refer to critical sources.

70. Anniko M, Wroblewski R. Ionic environment of cochlear hair cells. Hear Res. 1986;22:279-93. 71. Waltner JG, Raymond S. On the chemical composition of the human perilymph and endolymph. Laryngoscope. 1950;60(9):912-8. 72. Anson BJ, Winch TR, Warpeha RL, et al. The blood supply of the otic capsule of the human ear, with special reference to that of the cochlea. Ann Otol Rhinol Laryngol. 1966;75(4): 921-44. 73. Anson BJ, Warpeha RL, Rensink MJ. The gross and macro­scopic anatomy of the labyrinths. Ann Otol Rhinol Laryngol. 1968;77(4):583-607. 74. Mazzoni A. The vascular anatomy of the vestibular laby­ rinth in man. Acta Otolaryngol Suppl. 1990;472:1-83. 75. Spoendlin H. Anatomy of cochlear innervation. Am J Oto­ laryngol. 1985;6(6):453-67. 76. Wangemann P. K+ cycling and the endocochlear potential. Hear Res. 2002;165(1-2):1-9. Epub 2002/05/29. 77. Rhoton AL, Jr, Tedeschi H. Microsurgical anatomy of acoustic neuroma. Otolaryngol Clin North Am. 1992;25(2): 257-94. 78. Mazzoni A, Hansen CC. Surgical anatomy of the arteries of the internal auditory canal. Arch Otolaryngol. 1970;91(2): 128-35. 79. Silverstein H, Norrell H, Haberkamp T, et al. The unrecog­ nized rotation of the vestibular and cochlear nerves from the labyrinth to the brain stem: its implications to surgery of the eighth cranial nerve. Otolaryngol Head Neck Surg. 1986;95(5):543-9. 80. Mazzoni A. Internal auditory canal arterial relations at the porus acusticus. Ann Otol Rhinol Laryngol. 1969;78(4): 797-814. 81. Unel S, Yilmaz M, Albayram S, et al. Anastomoses of the vestibular, cochlear, and facial nerves. J Craniofac Surg. 2012;23(5):1358-61. 82. Pujol R, Lavigne-Rebillard M, Uziel A. Development of the human cochlea. Acta Otolaryngol Suppl. 1991;482:7-12; discussion 3. 83. Freeman S, Geal-Dor M, Sohmer H. Development of inner ear (cochlear and vestibular) function in the fetus-neonate. J Basic Clin Physiol Pharmacol. 1999;10(3):173-89. *84. Jackler RK, Luxford WM, House WF. Congenital malforma­ tions of the inner ear: a classification based on embryogen­ esis. Laryngoscope. 1987;97(3 Pt 2 Suppl 40):2-14. 85. Suehiro S, Sando I. Congenital anomalies of the inner ear: introducing a new classification of labyrinthine anomalies. Ann Otol Rhinol Laryngol Suppl. 1979;88(4 Pt 3 Suppl 59): 1-24. 86. Sennaroglu L, Saatci I. A new classification for cochleovesti­ bular malformations. Laryngoscope. 2002;112(12):2230-41. 87. Nieuwenhuys R. Anatomy of the auditory pathways, with emphasis on the brain stem. Adv Otorhinolaryngol. 1984; 34:25-38. 88. Borg E. Physiological mechanisms in auditory brainstemevoked response. Scand Audiol Suppl. 1981;13:11-22. 89. Miller CA, Brown CJ, Abbas PJ, et al. The clinical application of potentials evoked from the peripheral auditory system. Hear Res. 2008;242(1-2):184-97. 90. Luxon LM. The anatomy and pathology of the central auditory pathways. Br J Audiol. 1981;15(1):31-40.

CHAPTER

2

Evaluation of Auditory Function Janet Koehnke, Faith M Mogila, Maris Appelbaum, Joan Besing This chapter is designed to provide an overview of the profession of audiology. It begins with a brief history of audio­ logy followed by a description of the scope of practice of audiologists and some facts and figures on the incidence of hearing loss. The remainder of the chapter describes the diagnostic test procedures conducted by audiologists. These include subjective measures such as pure tone air conduction and bone conduction thresholds, speech recog­nition thresholds, and speech intelligibility tests as well as objective measures such as middle ear immittance, evoked otoacoustic emissions (OAEs), auditory brainstem tests, and vestibular tests. Each procedure is described briefly along with examples of typical test results and a discussion of the interpretation of results. The chapter concludes with some ideas about the future of audiologic assessment.

BRIEF HISTORY The profession of audiology emerged in the late 1940s as many soldiers from World War II returned home suffering from prolonged exposure to the sounds of artil­ lery, grenades, sirens, aircraft, and the like. The term itself was coined by three different individuals at about the same time in the mid-1940s, an otolaryngologist, Norton Canfield, a speech pathologist, Raymond Carhart, and an auditory scientist, Hallowell Davis.1 Shortly thereafter, specialized institutions were developed to serve the needs of military personnel returning from active duty who were experiencing difficulty hearing and understanding speech and hearing essential sounds such as alarms, honking horns, and other important auditory information.

Ch-2.indd 19

Since then the field of audiology has developed and grown into a flourishing profession, serving the needs of individuals across the lifespan who experience hearing and/or vestibular problems. Dr. James Jerger, one of Carhart’s first audiology students, was one of the pioneers of the profession; he developed many of the early test methods and procedures, including the Carhart-Jerger method for the measurement of pure-tone thresholds.2 This procedure is followed to this day and is the foundation of audiometric threshold testing that is the basis for all differential diagnosis in audiology. Dr. Jerger has also written a book entitled Audiology in the USA, which details the history and development of the profession.1 Audiology is the study of hearing and balance function and disorders; audiologists evaluate auditory and vesti­ bular function and provide rehabilitation for individuals across the lifespan identified with pathologies of these systems. It is also important to note that audiologists strive to inform and educate people about ways to prevent hear­ ing loss as well as cope with the challenges presented by their hearing loss. The professional activities of audiologists are clearly defined by the two largest organizations representing them, the American-Speech-Language-Hearing Associa­ tion (ASHA), and the American Academy of Audiology (AAA). In addition, all 50 states license or certify audio­ logists and have established guidelines for practicing in those states. According to the ASHA Scope of Practice for audiologists, “The practice of audiology includes both the prevention of and assessment of auditory, vestibular, and related impairments as well as the habilitation/rehabilitation and maintenance of persons with these impairments.

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The overall goal of the provision of audiology services should be to optimize and enhance the ability of an individual to hear, as well as to communicate in his/her every­ day or natural environment”.3 Similarly, the AAA Scope of Practice states, “Audiologists identify, assess, diagnose, and treat individuals with impairment of either peripheral or central auditory and/or vestibular function, and strive to prevent such impairments”.4 Both of these documents also stipulate that practicing audiologists must, at all times, adhere to the Code of Ethics of the respective organization.

SCOPE OF PRACTICE The scope of practice for the profession has grown dramatically over the past 30–40 years. It was not until 1977 that audiologists began dispensing hearing aids and other assistive devices. As technology has advanced, hearing aids have evolved from body worn analog devices to completely in-the-ear and small behind the ear digital devices. Along with the progress in hearing aid technology came the development of the cochlear implant and the bone anchored hearing aid in the 1960s. Cochlear implants have evolved from single channel devices that were first available commercially in 1972, to multiple channel systems that were introduced in 1984 and provide remarkably accurate auditory input to individuals with profound hearing loss.5 All of these advances in remediation have resulted in the expansion of the profession of audiology and the need for skilled audiologists. Although the middle latency response (MLR) and the late auditory evoked potentials (AEPs) were first discove­ red in the late 1950s, the introduction of clinical electro­ physiologic tests including auditory brainstem testing and evoked OAEs testing did not commence until the late 1970s. Together, these diagnostic procedures have contributed to the growth of the profession of audiology. More recently, audiologists have become involved in the evaluation and treatment of vestibular pathologies and in intraoperative monitoring of brainstem and cortical responses during surgical procedures. Clearly, audiology is a rapidly growing and developing profession. Currently, there are >12,000 audiologists in the United States.6 According to the US Bureau of Labor Statistics this number is expected to grow to about 17,000 by the year 2020.7 This is a rate of 37%, which is much more rapid than most professions. Audiologists work as independent practitioners in a variety of settings including private practice, schools, hospitals, community clinics, otolaryngology offices, industry, university clinics, and the military. They may also be involved in the education of audiology students as well

Ch-2.indd 20

as medical residents and interns and other health professionals. Audiologists serve a diverse population across the lifespan including individuals of all races, genders, religions, national origins, and sexual orientations.

DEMOGRAPHICS OF HEARING LOSS Along with the expanding breadth of the profession, there is an increased need for audiologists and audiologic services. This is, of course, due to the growing numbers of individuals with hearing loss. According to the National Institute on Deafness and Other Communicative Disorders (NIDCD) of the NIH, 17% (36 million) of American adults report some degree of hearing loss. More specifically, the NIDCD reports that “18 percent of American adults 45–64 years old, 30 percent of adults 65–74 years old, and 47 percent of adults 75 years old or older have a hearing loss”.8 World Health Organization statistics indicate that, worldwide, 360 million people (including 328 million adults and 32 million children) experience “disabling” hearing loss. They define disabling as “hearing loss >40 dB in the better hearing ear in adults and a hearing loss >30 dB in the better hearing ear in children”.9 In the newborn population, the incidence of hearing loss continues to be reported as two or three individuals per 1000 births in the United States.8 As a result of the 1993 NIH Consensus Conference on Newborn Screenings, programs to evaluate every newborn have been established in all 50 states. This has led to earlier identification of hearing loss and auditory pathologies, which, in turn, results in appropriate intervention at an earlier age. Despite earlier detection of hearing loss in newborns, according to Niskar et al.10, about 12.5% of children and adolescents in the United States aged 6–19 years (approximately 5.2 million) experience permanent hearing loss due to exposure to loud sounds. These numbers have likely increased in the past decade due to the use of personal listening systems and the popularity of clubbing and concert-going among teenagers and young adults. According to the NIDCD, approximately 15% of Americans age 20–69 have highfrequency hearing loss due to exposure to loud sounds or noise in some aspect of their daily lives.8 Other important statistics regarding hearing loss and auditory pathologies can be obtained from the NIDCD, the Centers for Disease Control, the World Health Organization, and the Hearing Health Foundation to name just a few sources. In our work as audiologists, it is imperative that we collaborate with other professionals to ensure that we provide the best possible care for our patients. Clearly, it is necessary for us to refer to and consult frequently with

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Chapter 2: Evaluation of Auditory Function otolaryngologists. By working together closely and conferring with each other, we can effectively monitor the auditory status of our patients. Individuals receiving implantable devices and those experiencing pathologies such as Meniere’s Disease, acoustic neuroma, or cholesteatoma represent just a few of the many individuals for whom collaborative care between audiologists and otolaryngo­ logists is so essential. Of course, there are many other health professionals with whom audiologists work on a regular basis. When diagnosing an infant with hearing loss it is imperative to consult with social workers, psychologists, and speechlanguage pathologists as well as physicians. For children with hearing loss, audiologists confer with teachers and other support personnel in the schools. Adults with gra­ dual or sudden onset hearing loss may need not only hearing aids or other assistive devices, but also help obtaining accommodations in the workplace. In such instances, audiologists are likely to interact with ��������������������� vocational counselors and possibly other individuals in state and local agencies to assist their patients. For geriatric patients, audiologists consult with home healthcare workers, personnel at senior centers and assisted living facilities, and others to achieve optimal auditory input in the environment where these individuals spend their time. Clearly, the overall goal is to work cooperatively to meet the needs of our patients.

CLINICAL AUDIOLOGIC PROCEDURES A complete audiologic evaluation typically includes asses­ sment, using insert or circumaural earphones, of pure-tone air and bone conduction thresholds as well as spondee thresholds and word recognition testing. In addition to these tests, an immittance battery and OAEs should always be included. The results of these procedures should provide comprehensive evidence for differential diagnosis. These findings also provide direction for habilitation/ rehabilitation of the patient. As with most clinical protocols, changes and adjustments in technique may be required to address any special needs or concerns of the patients. However, these adaptations should not sacrifice the fundamentals on which the following tests are designed and implemented.

Air and Bone Conduction Audiometric assessment is an integral component in otologic evaluation of a patient who is suspected of having an auditory and/or vestibular pathology. Testing should be completed by a state licensed audiologist in a quiet room

Ch-2.indd 21

21

Fig. 2.1: Typical audiogram form used to record audiometric air and bone conduction thresholds.

with minimal ambient noise. Test results may be recorded on a table or displayed on an audiogram such as the one shown in Figure 2.1. Prior to audiometric testing, a case history and oto­ scopy should be performed. Any obstruction in the outer ear could potentially affect pure tone responses. The tympanic membrane should be visible bilaterally during otoscopy. Obtaining a case history can provide informa­ tion to assist the audiologist in determining the order in which the tests are conducted. Optimally, air conduction, as well as bone conduction testing, is completed in a double-walled sound-treated booth with the patient wearing insert or circumaural earphones. All equipment utilized for testing should be calibrated annually. Air conduction stimuli pass through the outer, middle and ultimately, the inner ear on the way to the auditory cortex. Bone conduction stimuli are delivered directly to the cochlea through a bone oscillator placed on the mastoid bone. Pure tone signals are used to establish thresholds at specific frequencies. For air conduction, the octave frequencies from 250 to 8000 Hz are tested. In addition, if there is a 20 dB or greater difference between the thresholds at these adjacent frequencies, the interoctaves, 1500, 3000, and/or 6000 Hz, should be tested. Bone conduction thresholds are obtained in response to signals at the octave frequencies from 250 to 4000 Hz. Threshold testing should follow a standardized method such as those outlined by the American National Standards Institute,11 the American Speech-Language-Hearing Association,12 or the Carhart-Jerger procedure.2

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Once air conduction and bone conduction thresholds are obtained, it is standard clinical practice to calculate the pure tone average (PTA) for each ear. In most cases, this is the average of the pure tone air conduction thresholds at 500, 1000, and 2000 Hz. However, if the air conduction threshold at one of these three frequencies differs from the others by >20 dB, then a two frequency PTA is calculated using the two best thresholds at these three frequencies. It has been found that that this approach results in better agreement with the spondee recognition threshold (SRT) described below. In certain situations, the signal presented to the test ear is sufficiently intense to stimulate the cochlea of the nontest ear, causing inaccurate responses. This is known as crossover; the nontest ear actually responds when the tone is presented to the test ear. This occurs when the intensity of the test ear stimulus is at least 40 dB or greater (circumaural earphone) or 55 dB or greater (insert earphone) than the bone conduction threshold in the nontest ear. The term interaural attenuation is used to describe the amount of sound absorbed by the head before the sound presented to the test ear is intense enough to stimulate the opposite cochlea. The specific value varies as a function of frequency as well as the transducer used for testing. The values cited above are conservative estimates used clinically to ensure that crossover is not occurring during testing. To be certain the nontest ear is not being stimulated resulting in inaccurate responses, masking procedures must be employed. Thus, if the presentation level of the pure-tone in the test ear exceeds the bone conduction threshold in the nontest ear by these values (40 and 55 dB for circumaural and insert earphones, respectively), masking is presented to the nontest ear via air conduction using an insert or circumaural earphone. For bone conduction testing, the interaural attenuation is 10 dB. This means that if the bone conduction stimulus level and the air conduction threshold differ by >10 dB in the ear being tested or in the nontest ear, masking is necessary at that frequency. The reason for this value is because when a stimulus is presented via bone conduction, all of the bones in the skull are stimulated, not just the ones in the cochlea closest to the bone oscillator. The interaural attenuation is thus minimal resulting in the use of the 10 dB value for determining the need for masking. Use of appropriate masking techniques is essential to obtain accurate threshold measurements. Example audiograms are provided in Figures 2.2 to 2.5 to illustrate typical results obtained for bilateral and/or unilateral losses as well as conductive (Fig. 2.4), senso­ rineural (Fig. 2.2), mixed type hearing loss (Fig. 2.5), and

Ch-2.indd 22

a functional hearing loss (also referred to as malingering, Fig. 2.3). Each case includes results for pure tone air and bone conduction tests as well as many of the other tests described below such as OAEs, tympanometry, word recognition, etc.

Speech Testing The SRT is used as a reliability check for the pure tone findings. The PTA described above should be within +6 dB of the spondee threshold.13 The SRT is measured by pre­ senting two syllable words, called spondee words, with equal stress on each syllable. The words can be presented using either recorded speech or monitored live voice. Standardized testing procedures must be employed. The outcome of this measure is a threshold for speech and should be in good agreement with the average of the pure-tone thresholds at 500, 1000, and 2000 Hz (PTA). There may be times when traditional SRT testing cannot be employed. Examples of this might be with non-native speakers of English, infants, or difficult to test patients. In cases such as these, a speech detection threshold (SDT) or a speech awareness threshold (SAT) would be obtained. The preferred term according to ASHA14 is SDT because it is an accurate description of the task of exhibiting a behavioral change to spondee words or cold running speech. The SDT is often lower than the expected SRT because it requires the patient only to detect rather than recognize and correctly repeat speech stimuli. The other speech test typically administered is used to obtain the word recognition score (WRS), using monosyllabic words. This suprathreshold test should be administered 30–40 dB above the SRT.15 The goal of word recognition testing is to determine the best score a patient can attain. In some cases, this test may need to be administered at more than one intensity to find the level of maximum performance. This level is known as PB max (phonetically balanced) and is the highest speech recognition score that is determined using a PI function (performance intensity). According to Gelfand,16 speech recognition measures are used in every phase of audiology such as (1) to des­ cribe how hearing loss affects speech understanding, (2) in the differential diagnosis of auditory disorders, and (3) for determining the need for amplification and other forms of audiologic rehabilitation. Word recognition measures can also be used as part of a monitoring protocol, when needed. In patients with a sensorineural hearing loss, it is expected that the WRS will decrease as the severity of the loss increases. When dealing with a conductive loss, however, WRSs often approach the “excellent” range due to the normal bone conduction scores, when the words

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Chapter 2: Evaluation of Auditory Function

23

Fig. 2.2: Results for a 75-year-old patient. The pure tone results indicate a bilateral, symmetrical sensorineural hearing loss. Hearing thresholds are normal through 500 Hz, sloping to a mild sensorineural loss at 1000 and 2000 Hz, with a moderately severe loss at 8000 Hz. Good agreement between the PTA and SRT is noted. Immittance results indicate normal middle ear function. The patient has good word recognition scores bilaterally. TEOAE results indicate refer bilaterally. Audiologic recommendations for this patient would include hearing aids and perhaps other assistive devices. (PTA, pure-tone average; SRT, spondee recognition threshold; TEOAE. transient evoked otoacoustic emissions).

are presented at 30–40 dB above the SRT. In contrast, indi­viduals with cochlear pathology usually have WRSs between 60% and 90% when measured at the same relative level. Scores for this group vary widely depending upon the degree and configuration of hearing loss. For patients with retrocochlear pathologies, an often observed result is WRS much poorer than expected based on the degree of hearing loss. For example, a patient with a PTA of 30 dBHL may obtain a WRS of 54% when tested at 30 or 40 dB above the PTA. In addition to the traditional word lists used to obtain speech scores, there are other tests that can accomplish the

Ch-2.indd 23

same goal. When testing a child or a patient who is unable to verbally respond, tests such as the Word Intelligibility by Picture Identification—WIPI,17 Northwestern University Children’s Perception of Speech—NU-CHIPS,18 or Pedia­ tric Speech Intelligibility Test—PSI may be utilized.19 These tests require the patient to point to a picture in a closed set that cor­responds to the word they heard the audiologist speak. Tests also exist to assess how well a patient can hear in noise. In these tests, a target stimulus (word or sentence) is presented in the presence of background noise. Examples of these tests are the BKB-SIN, the QuickSIN and the Revised Speech Perception in Noise Test.20

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Fig. 2.3: These are results for a 15-year-old male who reported a sudden hearing loss in his left ear following an automobile accident. Test results were inconsistent. Right ear thresholds indicate normal hearing from 250 to 2000 Hz with a mild high frequency loss. Left ear results indicate a moderate hearing loss from 250 to 1000 Hz, sloping to moderately-severe from 2000 to 8000 Hz. Left ear thresholds reveal a shadow curve because interaural attenuation has been exceeded; therefore, crossover cannot be ruled out. The poor PTA–SRT agreement, normal tympanogram and acoustic reflexes, as well as “pass” OAE results for the left ear suggest that this patient is malingering. Recommendations for this patient would include a complete audiologic re-evaluation in 3–6 months. (PTA, pure-tone average; SRT, spondee recognition threshold; OAE, otoacoustic emission).

Immittance An integral part of a complete audiologic evaluation is the inclusion of the immittance test battery. Immittance protocols are used to evaluate middle ear status and the function of the ipsilateral and contralateral reflex patterns. Otoscopy should be performed prior to immittance to rule out any complications or pre-existing conditions that may contraindicate the use of this battery. Some examples of conditions that may preclude the use of tympanometry

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include a draining ear or cerumen that occludes the ear canal. The series of tests administered includes tympano­ metry, determination of the ipsilateral and contralateral reflex thresholds, and observation of reflex decay (if any). In order for the tests to be performed, a pneumatic seal between the probe assembly and the patient’s outer ear must be obtained. Failure to obtain a seal prevents completion of the test. Tympanometry is the first portion of the immittance battery. Once the seal is obtained, a probe tone is presented

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Fig. 2.4: Audiometric results for a 6-years-old with a history of chronic, recurrent otitis media. Pure tone thresholds in the right ear are within normal limits by air and bone conduction. Left ear thresholds indicate a mild flat conductive loss from 250 to 4000 Hz, gently rising to normal hearing at 8000 Hz. Note the excellent word recognition scores in the left ear, which are expected with a purely conductive loss. The air-bone gaps present from 250 to 4000 Hz in the left ear are also indicative of a conductive component. Tympanometry reveals negative pressure and reduced compliance in that ear. This patient “referred” on OAE results left ear, and “passed” right ear. Recommendations for this patient would include referral to an otolaryngologist. (OAE, otoacoustic emission).

to the patient’s outer ear and the pressure in the canal is varied to determine the point of maximum compliance of the middle ear system. The probe tone used for individuals over 6 months of age is 226 Hz, while a 1000 Hz probe tone is used for patients who are newborn to 6 months old. More information regarding the use of tympanometry in the pediatric population can be found in several pediatric audiology textbooks.21 Tympanograms are interpreted on several parameters: (1) ear canal volume, (2) equivalent peak pressure, and (3) static admittance. In more recent years, tympanometric

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width has been added to the parameters that are used in the assessment of middle ear function. Table 2.1 summarizes the normative data for these tympanometric para­meters described by ASHA.22 Interpretation of tympanometric width (or gradient) was introduced in 1968 by Brooks. It is a measure of the sharpness of the peak of the tympanogram. The gradient can be measured by bisecting the distance from the peak to the positive end of the tympanogram. Tympanometric width is reported in dekapascals (daPa). According to ASHA,22 the normal range is 60–150 daPa for children

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Fig. 2.5: These results are for a 55-year-old patient with a history of a mild sensorineural hearing loss. He came to the clinic complaining of stuffiness and pressure in the right ear. Left ear thresholds reveal a mild sensorineural loss from 250 to 2000 Hz, rising to normal hearing at 4000 Hz. Right ear thresholds reveal a moderate mixed loss at 250 and 500 Hz, sloping to a moderate loss at and above 1000 Hz. The air-bone gaps present from 250 to 4000 Hz, and the bone conduction thresholds >25 dBHL indicate a conductive component in that ear. Tympanometry reveals a flat configuration in the right ear, and a normal result in the left ear. TEOAE responses were “refer”, bilaterally. Recommendations for this patient should include referral to an otolaryngologist, and annual audiologic evaluations.

and 50–100 daPa for adults. Abnormal tympanometric width should be considered an indication of middle ear dysfunction.23 In 1970, Jerger introduced a classification system for tympanograms using a 226 Hz probe tone that is still in use today. Based on this system, tympanograms are characterized as either type A, Ad, As, C, or B.24 During tympanometry, the external ear canal pressure is changed from atmospheric pressure (0 daPa) to 200 daPa above the ambient pressure and down to 200–600 daPa below the ambient pressure. As would be expected, maximum compliance will be obtained when the pressure

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on each side of the tympanic membrane is the same. So, in order to evaluate middle ear status in a clinical population, the pressure in the outer ear is adjusted to find the point of maximum compliance. In some cases, there is no point of maximum compliance (Jerger type B). This is commonly seen in patients whose ears have middle ear effusion or have patent ventilating tubes in the tympanic membrane. In cases where the pressure in the external canal has to be a negative value to achieve maximum compliance, the tympanic membrane has been shown to be retracted into the middle ear space (Jerger type C).

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Table 2.1: Normative data for use in interpretation of tympanograms*

Type

Ear canal volume (ECV) in cc

Tympanometric peak pressure (daPa)†

Admittance (mmho)

A

0.6–1.5 (adults) 0.4–1.0 (children)

+100 to -100 daPa

0.3–1.4 mmho (adults) 0.2–0.9 mmho (children)

Ad

0.6–1.5 (adults) 0.4–1.0 (children)

+100 to -100 daPa

>1.4 mmho

As

0.6–1.5 (adults) 0.4–1.0 (children)

+100 to -100 daPa

100 dB SPL are considered elevated. Elevated or absent acoustic

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Fig. 2.6: Example of a normal, type A tympanogram. This is typically seen in individuals with normal hearing or sensorineural hearing loss. Note the peak at 0 daPa.

Fig. 2.7: Example of a hypermobile tympanic membrane, a type Ad tympanogram. This is typically seen in individuals with an ossicular discontinuity or a flaccid tympanic membrane. Note the peak at 0 daPa.

Fig. 2.8: Example of a hypomobile tympanic membrane, a type As tympanogram. This is typically seen in individuals with an otosclerosis. Note the peak at 0 daPa.

Fig. 2.9: Example of a middle ear with negative peak pressure, a type C tympanogram. This is typically seen in individuals with a retracted tympanic membrane. Note the peak at –300 daPa.

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Chapter 2: Evaluation of Auditory Function reflex thresholds in an individual with normal hearing or a sensorineural hearing loss may be indicative of a retrocochlear lesion and require further investigation. Acoustic reflex thresholds  40 dB in the better hearing ear.10 The estimated prevalence of disabling hearing loss in individuals aged 64 years and older by international region is presented in Figure 17.2. With the exception of the Middle East and North Africa region, all estimated prevalence rates fall between 30% and 50% for individuals 65 years of age and over. The highest prevalence rates for disabling hearing loss in adults over 65, according to this review, were noted in South Asia. Interestingly, on review of United States prevalence alone, racial differences in prevalence have been reported.11 When comparing individuals who classify themselves as black and white, statistically significant differences in the rates of hearing loss, defined as pure tone average in speech frequencies of >25 dB in the better hearing ear were noted. Overall prevalence of hearing loss in black males age 70 and older was noted as 48.3% (95% confidence interval: 36.3–60.3) versus 71.5% (95% confidence interval: 64.8–78.3) in white males (p = 0.002). Similar, prevalence differences were found among females age 70 years and older (p = 0.03): black females 39.8% (95% confidence interval: 20.6–59.1) versus white females 59.0% (95% confidence interval: 51.3–66.8). These findings are consistent with previous reports within the literature regarding a decreased prevalence of age-related hearing loss in black individuals.12-14 This is believed by some to be secondary to a hypothesized protective effect of increased melanin, particularly within the stria vascularis.15-17 Economic status has been noted to be correlated with the presentation of age-related hearing loss. This may be related to the multifactorial etiology of age-related hearing loss and the fact that undertreated otologic disease and systemic disease may contribute to hearing loss. Thus, indi­ viduals with improved socioeconomic status may have

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Chapter 17: Presbycusis access to more preventive care and therapeutic treatment preventing the onset or progression of hearing loss. According to the WHO study, greater overall increased income was correlated with a decreased prevalence of age-related hearing loss.10 Similar findings were reported by Lin et al. in a review of presbycusis prevalence in the United States.11 Genders have been found to impact the presentation of presbycusis. The male population appears to be more affected by age-related hearing loss as compared to their female counterparts. This has been identified in a number studies based both on self-reported subjective measures and objective audiometric data.1,18-20 In a data analysis of the National Health and Nutritional Examination Survey 2005–2006 cycle hearing assessment among 717 adults age 70 and older, a statistically significant difference in the rate of presbycusis (defined as speech frequency pure tone average of >25 dB in the better hearing ear) was noted in males as compared to females (69.8% and 58.2%, respectively).11

Etiology As presbycusis represents the sum of life influences that precipitate the presentation of hearing loss with aging, there are a number of factors that have been associated with the development of presbycusis. Gates poignantly describes presbycusis as “a mixture of acquired audi­tory stresses, trauma, and otologic diseases superimposed upon an intrinsic, genetically controlled, aging process”.21 The etiology of presbycusis is influenced by genetics (up to 50% have significant family history), cardiovascular health (in turn influenced by smoking and diabetes), history of noise exposure, as well as ototoxic exposure and otologic disorders.22

Aging and Oxidative Injury In a landmark article by Denham Harman in 1956, the free-radical theory of aging was introduced.23 Since that time, free radical damage has been implicated as an etiologic factor in various organ systems, including the ophthalmologic, integumentary, and hepatic systems.24-27 Similarly, oxidative stress has been hypothesized to be an integrally involved etiological factor in the development of presbycusis via free radical (reactive oxygen species and reactive nitrogen species) associated mitochondrial dys­ function.28 Various findings have been identified in animal

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studies to support this theory. Increased markers of oxida­ tive stress have been noted to be increased in the cochlea of aged CBA/J mice.29 Mice missing the gene encoding Cu/Zn superoxide dismutase, a critical enzyme in the reduction of reactive oxygen species and maintenance of oxidative balance show premature presbycusis.30,31 Simila­rly, over­ expression of mitochondria-localized catalase that elimi­ nates reactive oxygen species has been demonstrated to be protective against age-related threshold shift.32 It is post­ ulated that with the accumulation of mitochondrial DNA mutation, oxidative phosphorylation is impaired and expression of antioxidant enzymes is altered, leading to further increase in reactive oxygen species in the cochlea.33 Human temporal bone studies support these findings. Various deletions within the mitochondrial genome have been noted in human temporal bone tissue.34-38 A correla­ tion has been identified between the extent of age-related threshold shifts and mitochondrial DNA deletions. 34,37

Noise Noise exposure is a well-established risk factor for hear­ ing loss.14 Noise exposure not only contributes to oxidative stress and the production of reactive oxygen species that mediates short-term injury but also may contribute to long-term damage. Hearing loss from noise exposure, also known as noise-induced hearing loss, may take the form of transient threshold shifts or long-term acoustic changes. Everyday noise exposure can cause hearing loss and may accelerate the process that leading to presbycusis. Table 17.2 presents the current National Institute for Occupation­ al Safety and Health (NIOSH) and Occupational Safety and Health Administration (OSHA) guidelines for noise exposure. To put these noise level exposures into perspec­ tive, Table 17.3������������������������������������������ provides a list of commonly and less com­ monly encountered noises with associated noise levels. It is interesting to note that listening to high power head­ phones on a near maximum level for a period of 1 hour in the gym or on a long commute, attending a con­ cert, or using the snow blower for over 30 minutes may exceed the current NIOSH recommendations for noise exposure. It is easy to see how simple life experiences may contribute to noise damage over time. Remarkably, recent studies have demonstrated that the effect of noise-induced hearing loss may extend long after the exposure has stopped.39 Noise damage occurs even with temporary or no immediate hearing loss, which is believed to contribute to accelerated presbycusis. This

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Table 17.2: National Institute for Occupational Safety and Health (NIOSH) and Occupational Safety and Health Administration (OSHA) recommended permissible noise exposure levels

Permissible noise level exposure NIOSH (dB)

OSHA (dB)

8

85

90

6

86

92

4

88

95

3

89

97

2

90

100

1.5

92

102

1

94

105

Sound level (dB)

Rustling leaves

20

Whisper at 6 ft

30

Residential area at night

40

Quiet office

50

Normal conversation

60–65

Car noise

70

City traffic

85

Lawnmower

90 95

0.5

97

110

Subway train at 200 ft

0.25

100

115

Hand drill

95–100

0

112

 

Snowmobile

100

Motorcycle

100

Power mower

105

Jackhammer

110

Power saw

110

Sandblaster

115

Maximum volume ear buds

85–115

Ambulance siren

120

Loud concert

100–125

Pneumatic riveter

125

Jet engine

140

0.22 Caliber riffle

145

12 Gauge shotgun

165

0.357 Caliber revolver

170–175

is supported by findings in animal models of hearing loss demonstrating permanent neuronal losses in the spiral ganglion correlated with accelerated age-related hearing loss40-42 and loss of synaptic terminal between inner hair cells and spiral ganglion neurons.41,43 In clinical studies, presbycusis has been found to be more severe in indi­ viduals thought to have suffered cochlear damage in their youth from noise exposure.39 It is important to note that presbycusis can develop in patients without a history of excessive noise exposure. Additionally, the shape and progression of hearing loss may differ in individuals with significant noise exposure. Gates et al. found that in subjects with noise induced threshold shifts, there is a reduced progression of hearing loss at 3, 4, and 6 kHz and accelerated hearing loss at the surrounding frequencies, particularly 2 kHz, with age, which is the reverse of that seen in individuals without previous significant noise exposure.39 Not only does noise exposure contribute to the development of presbycusis, it also impacts the character of threshold shifts associated with presbycusis.

Hereditary Factors Heredity is an important factor in age-related hearing loss. A strong familial association has been implicated in presbycusis. This familial association implying poten­ tial genetic susceptibility to age-related hearing loss.44,45 App­rox­imately 30–50% of variance in presbycusis is attri­ buted to the effects of genes.45,46 Various candidate genes

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Environmental sounds Stimulus

Sound level Hours per day

Table 17.3: Commonly and less commonly encountered environmental sounds

Purple: Within the cautionary range for limited noise exposure. Gray: Within the cautionary range for immediate noise injury.

have been proposed; however, there currently is no widely accepted genetic etiology that has been identified. The multifactorial nature of the etiology of presbycusis poses a challenge in the identification of genetic contribution to this disease process in clinical studies.

Additional Etiological Factors As presbycusis represents the progression of hearing loss with aging, various additional factors have been identified that affect the development and progression of presbycu­ sis. Table 17.4 describes additional etiological factors that have been proposed in the development of age-related

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Chapter 17: Presbycusis Table 17.4: Factors contributing to presbycusis

Factor

Exposures

Environmental

•• Noise

 

•• Low socioeconomic status

Chemical exposures

•• Toluene

 

•• Trichloroethylene

 

•• Styrene

Otologic disease

•• Otosclerosis

 

•• Chronic otomastoiditis

 

•• Temporal bone trauma

 

•• Meniere’s

Medications

•• Aminoglycosides

 

•• Platinum-based chemotherapeutic agents

 

•• Loop diuretics

 

•• Phosphodiesterase type 5 inhibitors

 

•• Salicylate

Habitual

•• Tobacco*

 

•• Alcohol abuse*

Systemic disease

•• Renal failure

 

•• Diabetes

 

•• Cardiovascular disease

 

•• Immunodeficiency

Protective factors

•• Estrogen

 

•• High bone mineral density

 

•• Caloric restriction*

 

•• Aldosterone

*Conflicting reports in the literature.

hearing loss.5,7,40-43,47-70 One major contributing factor is otologic disease. In theory, any otologic condition that precipitates hearing loss throughout life will contribute to the progression of age-related hearing loss. Studies in the literature have highlighted the etiologic contribution of otosclerosis, chronic otitis, Meniere’s and temporal bone trauma or head trauma to the presentation of age-related hearing loss.54,71,72 In addition to otologic disease, ototoxins have been described as a contributing factor in the etiol­ ogy of age-related hearing loss, namely aminoglycosides (e.g. gentamicin and streptomycin), platinum-based chemotherapeutic agents (e.g. cisplatin and carboplatin), high-dose loop diuretics, and salicylate and phosphodi­ esterase type 5 inhibitors (e.g. sildenafil, vardenafil, and tadalafil).65-70,73,74 Additionally, toxic exposures to heavy metals (e.g. lead and mercury) and solvents (e.g. toluene, styrene, and xylene) have been implicated as poten­ tial contributing factors for age-related hearing loss.59-62

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Tobacco and alcohol abuse have been proposed as etio­ logic factors in presbycusis; how­ever, there are conflicting reports within the literature in this regard.55,63,64 In multiple studies, cardiovascular disease and diabetes have been associated with the progression of presbycusis.5,47,49,56,57,75,76 Additionally, renal failure and impaired immune function may play a contributing role.53,58 A number of factors have been found to be protective against the progression of age-related threshold shift. Hormonal function, including aldosterone and estrogen, have been found to protective against age-related changes in hearing.48,77 Higher levels of bone mineral density have been correlated with decreased rate of change in hearing with age.55 Additionally, caloric restriction may play a preventive role.7,52 Further study would be required to fully elucidate these effects.

Impact of Presbycusis The impact of age-related hearing loss is not limited to merely the ability of an individual to hearing and com­ prehend speech. The impact of presbycusis is far reach­ ing. It not only impacts the individual from a psychosocial perspective and potentially increases the progression of dementia, but it also has a significant public health impact internationally.

Psychosocial Impact The psychosocial impact of presbycusis has been well established. With progression, presbycusis typically pre­ cipitates difficulty with speech discrimination and word understanding, particularly in ambient situations. This translates to difficulty participating in conversation at a busy restaurant or understanding the punch line of a joke at a family gathering. Although this may seem minor, for many individual this can produce significant embarrass­ ment and frustration. Social isolation and anxiety in social situation have been described in association.78,79 In count­ less patients, this progresses to decreased autonomy and depression, significantly impacting their activity level and social interconnectivity.79-85 This has been associated with a significant decline in overall quality of life reported by individuals affected by presbycusis.86,87

Association with Dementia The association between dementia and age-related hear­ ing loss has been described for decades within the lite­ rature. However, our understanding of the impact that

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presbycusis plays on the progression of dementia has evolved significantly. Within the mid-1980s, various pub­ lications revealed the significant correlation between hearing impairment in the elderly and the progres­ sion of dementia.80,88,89 Global functional decline also has been noted in association with age-related hearing loss, shy of the clinical diagnosis of dementia within this population.78,90,91 A direct positive correlation between degree of hearing loss and cognitive decline has been noted on both verbal and nonverbal cognitive testing in numerous reports in the literature.55,80,92-97 More recen­ tly, this association has been further quantified. Among indivi­duals free of prevalent dementia or mild cognitive impair­ment, impact of degree of hearing loss was quan­ titatively associated with decline in cognitive function. It was noted that a 25 dB hearing loss produces a decline equivalent to an age difference of 6.8 years on test of executive function.98,99 Additional study is require to fur­ ther investigate this potential causative relationship.

Public Health Impact Presbycusis poses a significant public health concern inter­ nationally. The percentage of the population over the age of 65 is projected to grow internationally over the new few decades.100 As such, the prevalence of age relating hear­ ing loss will increase precipitously. According to the WHO hearing loss is one of the six leading contributors to the burden of disease in industrialized countries (WHO, 2000). Based upon the WHO 2012 Hearing Loss Estimate, adults make up 91% of individuals internationally with disabling hearing loss, accounting for 328 million of 360 million total individuals internationally affected (disabling hearing loss defined as ≥40 dB of hearing loss).10 Adults over the age of 64 years make up more than half of all adults with hearing loss.101 It is projected by 2025 that there will be 1.2 billion people over 60 years of age worldwide, with >500 million individuals who will suffer significant impairment from presbycusis.102 Presbycusis may contribute to early unde­ sired retirement and decreased workforce participation, creating a significant economic impact.

Pathophysiology Pathophysiological changes have been noted in various components of the auditory system in association with age-related hearing loss. Traditionally, presbycusis was believed to be a disorder of the peripheral auditory sys­ tem, namely the cochlea. Schuknecht developed a classi­ fication system that highlights the cochlear changes

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that have been noted in association with age-related hearing.103,103a. Figures 17.3A to D depicts audiograms that would accompany four of the classic classifications of presbycusis proposed by Schuknecht. Sensory presbycu­ sis is characterized by slowly progressive, bilateral steep down-sloping high-frequency hearing loss asso­ ciated with loss of cochlear hair cells, particularly at the basal turn of the cochlea. Neural presbycusis is characterized by decline in speech discrimination associated with spiral ganglion cell loss. Metabolic presbycusis is characterized by flat hearing loss attributed to atrophy within the stria vascularis. Mechanical presbycusis is associated with a gradual descending pattern of hearing loss presumed to occur as a function of stiffening of the basilar membrane. The most common form encountered is mixed presby­ cusis that encompasses flat, sloping, or high-frequency hearing loss and is associated with a combination of hair cell, spiral ganglion, and strial losses.104 In addition to the histopathologic changes described within the Schuknecht classification system, various cochlear changes have been described in association with aging, including loss of outer hair cells and support cells, changes in hair cell stereo­ cilia, vascular changes in the stria vascularis, decreased synapses, particularly at the basal turn, and loss of nerve fibers and ganglion cells.105-110 In addition to the previously proposed peripheral histopathology related to age-related hearing loss, recent evidence supports a central compo­ nent to age-related hearing loss, citing the fact that audi­ tory performance in elderly individuals is largely impacted by decreased spiral ganglion cells, decreased central plasticity, central auditory processing disorder, as well as increased incidence of central nervous system disease and cognitive decline.22,111 Central presbycusis likely represents a component of the overall presentation of presbycusis rather than an isolated entity in and of itself.112 Further study is required to better characterize the central compo­ nent of presbycusis.

Clinical Evaluation The clinical evaluation of patients present with age-related hearing loss often begins with the primary care provider. Primary care providers, including gerontologists, are typi­ cally charged with the responsibility of coordinating the care of elderly patients. Referral for audiometric evalua­ tion should be included in the routine evaluation of the geriatric patients. This appears as one of the goals of the United States National Institutes of Health (NIH) Healthy People 2020 (ENT-VSL-5: increase the number of persons

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Fig. 17.3A: Pure tone audiogram characteristic of the various classes of presbycusis described by Schuknecht with illustration of proposed region of cochlear involvement. (A) Sensory presbycusis. The audiogram depicts the typical shape of hearing loss associated with sensory presbycusis, which is postulated to be secondary to hair cell loss.

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Fig. 17.3B: Neural presbycusis. The audiogram depicts the typical high frequency of hearing loss associated with neural presbycusis that is postulated to be secondary to loss of spiral ganglion cells. The key change noted with neural presbycusis is decline in speech discrimination.

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Fig. 17.3C: Metabolic presbycusis. The audiogram depicts the typical flat hearing loss associated with metabolic presbycusis that is postulated to be secondary to atrophy within the stria vascularis.

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Fig. 17.3D: Mechanical presbycusis. The audiogram depicts the typical gradual sloping shape of hearing loss associated with mechanical presbycusis that is postulated to be secondary to stiffening of the basilar membrane.

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who are referred by their primary care physician or other health care provider for hearing evaluation and treat­ ment).113 It is essential to realize that individuals with early presbycusis may minimize their symptoms. Patients with presbycusis may initially be reluctant to admit that they are experiencing hearing loss. Alternatively, some individuals view hearing loss as a normal process of aging “like wrin­ kles” or perceive it as something that they suffer through. Therefore, regardless of patient report among the geriatric population, referral for audiometric evaluation should be made at least every 5 years. This is in accordance with the NIH Healthy People 2020 objective ENT-VSL-4 that aspires to increase the proportion of persons who have had hear­ ing examination on schedule, which is suggested as within a 5-year period.113 On clinical presentation, patients typically present with high-frequency sensorineural hearing loss accom­ panied by decline in speech discrimination and speech understanding. Patients may report particular difficulty understanding conversation in ambient conditions. They may report complaints or their family may report that they complain that other tend to mumble or slur their words. Individuals with presbycusis often report that men’s voices are easier to hear and understand than women’s and children’s. A major related complaint of patients with presbycusis is associated tinnitus. As the hearing loss progresses, tinnitus tends to progress as well. The tinnitus may present as intermittent, but typically becomes constant with progression of hearing loss. The clinical evaluation of patient should include a complete head and neck examination with cranial nerve evaluation and otologic evaluation. Audiometric evalua­ tion should be performed, including pure tone audiom­ etry, speech discrimination, tympanometry, and acoustic reflexes. Typical findings are of high-frequency sensorineu­ ral hearing loss that is symmetric. Imaging of the temporal bone or skull base is typically not indicated with normal otologic examination and characteristic audiometric find­ ings. If asymmetric hearing loss or otologic abnormalities, are noted, clinical discretion should direct imaging.

Prevention of noise trauma is a major component of prevention of age-related hearing loss. Patients should avoid excessive noise exposure. When noise exposure is unavoidable (e.g. occupational requirements or recre­ ation), adequate noise protective equipment should be utilized to dampen noise exposures. Inserted ear plugs provide approximately 15–25 dB of sound attenuation. Alternatively, noise protection ear muffs provide approxi­ mately 20–30 dB of sound attenuation. For individuals with high acoustic professional demand with significant noise exposure (i.e. musicians, music teachers, recording engineers or sound crew members), high fidelity hear­ ing protection or musicians ear plugs are recommended. These customized ear plugs reduce sound levels presented to the ear while maintaining clear and nature sound with­ out a muffled character as experienced with traditional ear plugs. The level of attenuation too is customizable.

Prevention

Auditory Assistive Devices

The key to prevention of age-related hearing loss is avoid­ ance of factors that can promote or accelerate its pro­ gression. Adequate treatment of potentially contributing otologic disease should be employed. Ototoxins should be avoided when possible. Potential contributing comorbidi­ ties should actively and aggressively be managed to pre­ vent associated threshold shifts.

Hearing assistive devices are nonprescription, nonpersonal­ ized aids that augment environmental sounds or pro­ vide alternatives to challenging acoustic situation. These aids include such devices as telephone amplifiers, tele­ vision amplifiers, alarm clocks with vibrators, frequencymodulation transmitters, doorbell signalers, and modified smoke detectors. These devices are of great benefit to

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MANAGEMENT The mainstay of management of age-related hearing loss is environmental optimization and auditory rehabilita­ tion. Auditory rehabilitation takes many forms, ranging from simple assistive devices to cochlear implantation. Currently there are no medical therapies available for the treatment or prevention of age-related hearing loss. This presents a significant opportunity for future research and development.

Environmental Optimization Patients with presbycusis, whenever possible, should make modifications to their environment to optimize their audi­tory milieu. This may take the form of turning off tele­ visions or decreasing the volume of background music during dinner conversations or sitting in a favorable loca­ tion to facilitate face to face conversation to allow not only lip reading but also the use of nonverbal cues (i.e. facial expression and gestures) to augment speech understand­ ing. If comfortable, individuals may request speakers to speak more slowly as comprehension of rapid speakers is commonly impaired in individuals with presbycusis.

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patient with age-related hearing loss, but are limited in their ability to assist in the most challenging of communi­ cation situations.

Hearing Aids Hearing aids represent the mainstay of treatment for agerelated hearing loss. Hearing aids are typically recom­ mended for sound amplification in individuals with hearing thresholds within the speech frequencies of 40 dB or greater. In selective cases where employment or educa­ tional demands are unusually demanding, losses of  60 years, established voluntary hearing safety programs and have virtually no OHL in their employees. The history of the OSHA Noise Regulation and of the Hearing Conservation Amendment is complex, as with most other important regulations and laws. Compara­ tively little valid and reliable scientific data were available on which to base a noise stan­dard. Practical measures, politics, economics, and numerous other factors played important roles in determining the final regulation. Discussion and review of the most important features of OSHA’s

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requirements are detailed elsewhere.1 The most recent final OSHA ruling, complete details of which are listed in the Federal Register, Vol. 67, No. 126, July 1, 2002, details the requirements for recording hearing loss. The register contains Occupational Safety and Health Adminis­tration Regulation 29 CFR 1904, Occu­pational Injury and Illness Recording and Reporting Requirements, Final Rule, which became effective January 1, 2003. It requires the reporting of hearing losses that have a minimum of a 10 dB shift in hearing acuity for the average of 2000, 3000, and 4000 Hz when compared with baseline (known as a Standard Threshold Shift) resulting in hearing thresholds over 25 dB.

Development of a Noise Standard Comprehensive understanding of the nature of OHL has been hindered by the difficulties associated with scientific studies in an industrial setting. A brief review of old literature and an in-depth discussion of more comprehensive and more recent studies highlights the complexities of the problem and the clinical and scientific findings that form the basis for the guidelines set forth in this chapter. In 1952, James H. Sterner conducted an opinion poll among a large number of individuals working with noise and hearing investigating the maximum intensity level of industrial noise that they considered safe to hearing2 (Fig. 18.1). The wide range of estimates demonstrated clearly the lack of agreement even among knowledgeable individuals and the futility of any attempt to establish meaningful guidelines by means of such polls. In 1954, the Z24-X-2 Subcommittee of American Standards Association (now ANSI) published its exploratory

Fig. 18.1: Estimates of “safe” frequency intensity levels.

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Chapter 18: Occupational Hearing Loss report on the relations of hearing loss to noise exposure.3 On the basis of available data, they could not establish a “line” between safe and unsafe noise exposure. They presented questions that required answers before criteria could be formulated, including: (a) What amount of hearing loss constitutes a sufficient handicap to be considered undesirable? (b) What percentage of workers should a standard be designed to protect? The report emphasized the need for considerably more research before “safe” intensity levels could be determined. Many authors between 1950 and 1971 proposed damage risk criteria, only some of which were based on stated protection goals. Articles are referenced in Table IX of NIOSH’s Criteria for Occupational Exposure to Noise.4 All these reports had limitations that precluded the adoption of any one of them as a basis for the establishment of standards. In 1973, Baughn5 published an analysis of 6835 audiograms from employees in an automobile stamping plant, with employees divided into three groups on the basis of estimated intensity of noise exposure. Its validity as the basis for a national noise standard was seriously questioned by Ward and Glorig6 and others because of shortcomings of nonsteady-state noise exposures, vague estimates of noise dosage, auditory fatigue, and test room noise. Baughn’s raw data were never made available to the Secretary of Labor’s Advisory Committee for Noise Standard despite a formal request from that group. A study by Burns and Robinson7 avoided many of the deficiencies of previous studies but was based on a very small number of subjects exposed to continuous steadystate noise, particularly in the 82–92 dBA range. The study included workers who “change position from time to time using noisy hand tools for fettling, chipping, burnish­ing, or welding”—hardly continuous or steady state. Their report admitted to the inclusion of workers exposed to nonsteady-state levels under 90 dBA. In fact, some workers were included whose noise exposures varied by 15 dBA. The oft-quoted Passchier-Vermeer report8 was not based on an actual field investigation but was rather a review of published studies up to 1967. Some of these studies addressed the validity of measuring sound levels in dBA; none was really designed to be used as the basis for a noise standard. As early as 1970, interested individuals from industry, labor, government, and scientific organizations discussed the concept of an interindustry noise study. The project was started in 1974 for the stated purpose of gathering data on the effect of steady-state noise in the range of 82–92 dBA. While the results of such a study would obviously be

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of interest to those involved in noise regulation, the basic purpose of the study was scientific rather than regulatory. The detailed protocol has been published6 and will not be repeated here. Some of the important points were: (a) Clear definitions of the temporal and spectral characteristics of the noise. (b) Noise exposures had to fall between 82 and 92 dBA, with no subject exceeding a 5-dBA range (later modified to a 6-dBA range). (c) Noise environment had to be steady state throughout a full shift, with few, if any, sharp peaks of impact noise. (d) Subjects, both experimental and control, had to include men and women. (e) No prior job exposure to noise over 92 dBA for experimentals and 75 dBA for controls. (f ) Minimum of 3 years on present job. (g) All audiometric testing, noise measurement, equipment calibration, otological examinations, histories, and data handling had to be done in a standardized manner, as detailed in the protocol. (h) The original raw data had to be made available to all serious investigators upon request at the conclusion of the study. Hearing levels were measured in 155 men and 193 women exposed to noise levels ranging from 82 to 92 dBA for at least 3 years, with a median duration of ~15 years; they were also measured in 96 men and 132 women with job exposure that did not exceed 75 dBA. Noise exposure was considered steady state in that it did not fluctuate >3 dB from the midpoint as of the time of the first audiogram. As many subjects as possible were re-examined 1 year later and 2 years later. Jobs involving some 250,000 employees were examined to find the 348 experimen­tal subjects who met the criteria of the inter-industry noise study as of the time of entry. Within the range of 82–92 dBA, differences in noise intensity had no observable “effect” on hearing level. That is, the hearing levels of workers at the upper end of the noise intensity exposure were not observably different from the hearing levels of workers at the lower end of the noise exposure. Age was a more important factor than duration on the job in explaining differences in hearing level within any group. Comparisons between experimental and control subjects were made on an age-adjusted basis. Differences between women exposed to 82–92 dBA and their controls were small and were not statistically significant. Differences between men exposed to 82–92 dBA and their controls were small and were not statisti­ cally significant at 500, 1000, and 2000 Hz. Levels in the noise-exposed group significantly exceeded those in the control group at 3000, 4000, and 6000 Hz by 6–9 dB. At 8000 Hz, differences again became not significant.

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There was no real evidence of a difference between noise-exposed workers and their controls with respect to the changes in hearing level during the course of follow-up 1 and 2 years after initial audiograms. Changes were negligible for both groups. It is important to note that the studies discussed and the regulations promulgated to date concern themselves with exposure to continuous noise. More recent research demonstrated that intermittent exposure to noise results in different effects on hearing.9 Although it may produce marked, high frequency, sensorineural hearing loss, intermittent noise does not have the same propensity to spread to the speech frequencies even after many years of exposure, as happens with continuous noise exposure.

Disability and Impairment Methods for compensating people with OHL vary from jurisdiction to jurisdiction.1 An essential part of a compensation act is the manner of calculating how much compensation an employee should receive for a specific amount of hearing loss. It is first necessary to distinguish among impairment, disability, and handicap. Impairment is a medical concept meaning a deviation from normal. Disability and handicap involve many nonmedical factors and include a concept of loss of ability to earn a daily livelihood, “loss of living power” or reduction of the individual’s enjoyment of daily living. Hearing impairment contributes to a disability, but many other factors are involved. Compensation is awarded for disability.

CHARACTERISTICS OF OHL Audiometric Features OHL is a specific disease due to repetitive injury with established symptoms and objective findings. The diagnosis of OHL cannot be reached reliably solely on the basis of an audiogram showing high-frequency sensorineural loss and a patient’s history that he/she worked in a noisy plant. Accurate diagnosis requires a careful and complete history, physical examination, and often laboratory, imaging, and special audiologic studies. Numerous entities such as acoustic neuroma, labyrinthitis, ototoxicity, viral infections, acoustic trauma (explosion), head trauma, hereditary hearing loss, diabetes, presbycusis, autoimmune and genetic causes must be ruled out, as they are responsible for similar hearing loss in millions of people who were never employed in noisy industries.

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The American College of Occupational Medicine Noise and Hearing Conservation Committee promulgated a position statement on the distinguishing features of occu­ pational noise-induced hearing loss.10,11 This statement summarized the accepted opinions of the medical community regarding diagnosis of OHL. The American Occu­ pational Medicine Association (AOMA) Committee defined occupational noise-induced hearing loss as a slowly deve­ loping hearing loss over a long time period (several years) as the result of exposure to continuous or intermittent loud noise. The committee stated that the diagnosis of noiseinduced hearing loss is made clinically by a physician and should include study of the noise exposure history. It is also distinguished OHL from acoustic trauma, an immediate change in hearing resulting from a single exposure to a sudden burst of sound, such as an explosive blast. The committee recognized that the principle character­istics of occupational noise-induced hearing loss are as follows: 1. It is always sensorineural affecting the hair cells in the inner ear 2. It is almost always bilateral. Audiometric patterns are usually similar bilaterally 3. It almost never produces a profound hearing loss. Usually, low-frequency limits are 40 dB and high-frequency limits 75 dB 4. Once the exposure to noise is discontinued, there is no substantial further progression of hearing loss as a result of the noise exposure 5. Previous noise-induced hearing loss does not make the ear more sensitive to future noise exposure. As the hearing threshold increases, the rate of loss decreases 6. The earliest damage to the inner ears reflects a loss at 3000, 4000, and 6000 Hz. There is always far more loss at 3000, 4000, and 6000 Hz than at 500, 1000, and 2000 Hz. The greatest loss usually occurs at 4000 Hz. The higher and lower frequencies take longer to be affected than the 3000–6000 Hz range 7. Given stable exposure conditions, losses at 3000, 4000, and 6000 Hz will usually reach a maximal level in 10–15 years 8. Continuous noise exposure over the years is more damaging than interrupted exposure to noise, which permits the ear to have a rest period. Since that time, the criteria have been updated twice.12,13 The most recent guidance statement from the American College of Occupational and Environmental Medicine is considerably more extensive.13 It includes a list of characteristics and additional consideration associated

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Chapter 18: Occupational Hearing Loss with noise-induced hearing loss. In summary, the current list of characteristics of noise-induced hearing loss includes the following: 1. It is always sensorineural, affecting primarily the cochlear hair cells 2. It is typically bilateral 3. The first audiometric sign is “notching” between 3000 Hz and 6000 Hz with recovery at 8000 Hz 4. Noise exposure alone usually does not produce hearing loss >75 dB in the high frequencies and 40 dB in the lower frequencies 5. Hearing loss due to noise increases most rapidly during the first 10–15 years of exposure 6. Ears previously exposed to noise are not more sensitive to future noise exposure 7. There is no conclusive evidence that hearing loss due to noise progresses once the noise exposure has been discontinued 8. The risk of noise-induced hearing loss is low at exposures below 85 dBA TWA but increases as exposures rise above this level 9. Continuous noise exposure is more damaging than intermittent noise exposure 10. Hearing protectors provide less attenuation than suggested by the noise reduction rating. Hearing protectors should be selected to reduce exposure to 85%) in a quiet room. If patients have much lower discrimination scores, another cause in addition to OHL should be suspected.

Gradual Hearing Loss with Early Onset In addition to having the characteristics of a bilateral sensorineural hearing loss with a 4000 Hz dip, OHL begins early with noise exposure and progresses gradually. Sudden deafness is not caused by noise to which a patient is exposed regularly at his/her job. There are, of course, incidents of unilateral sudden deafness due to acoustic trauma from an explosion or similar circumstance. Other causes must be sought in sudden deafness in one or both ears regardless of occupational noise exposure. OHL characteristically develops during the first few years of exposure and may worsen over the next 12–15 years

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Chapter 18: Occupational Hearing Loss of continued exposure, but the damage does not continue to progress rapidly or substantially with additional exposure beyond 12–15 years. Rarely, an employee working in consistent noise will have good hearing for 4 or 5 years and then develop progressive hearing loss from occupational causes. Employees who retire after age 60 and develop additional hearing loss without continued noise exposure generally should not attribute this to their past jobs.25 The same pertains to employees who wear hearing protectors effectively and either develop hearing loss or have additional hearing loss. Accurate diagnosis is important because some such hearing losses occur from etiologies that are amenable to treatment.

Asymptotic Hearing Loss Another characteristic of OHL is that specific noisy jobs produce a maximum degree of hearing loss. This has been called asymptotic loss. For example, employees using jackhammers develop severe high frequency, but minimal low fre­quency, hearing losses. Employees working for years in 92 dBA generally do not have > 20-dB losses in the low frequencies and once they reach a certain degree of high-frequency hearing loss, little additional loss occurs. Many employees exposed to weaving looms experience a maximum of 40-dB loss in the speech frequencies, but they rarely have greater losses. This is believed to be due to the hearing impairment itself protecting the ear from further damage. For example, if someone with a 35-dB hearing loss is exposed to a 95-dB sound, he hears only 60 dB (in the absence of loudness recruitment), and little or no additional noise-induced hair cell damage occurs. If an employee shows a loss much greater than is typical for similar exposure, the otologist should suspect other causes.

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Other Causes of the 4000-Hz Dip Viral Infections It is well known that viral upper-respiratory infections may be associated with hearing loss, tinnitus, and aural fullness. This fullness is frequently due to inner-ear involvement rather than middle-ear dysfunction. Viral cochleitis also may produce either temporary or permanent sensorineural hearing losses, which can have a variety of audiometric patterns, including a 4000-Hz dip (Fig. 18.4).26 In addition to viral respiratory infections as causes of sensorineural hearing loss, rubella, measles, mumps, cytomegalic inclusion disease, herpes, and other viruses have been implicated (Fig. 18.5).

Skull Trauma Severe head trauma that results in fracture of the cochlea usually produces profound hearing loss or total deaf­ ness. However, lesser trauma to the inner ear may produce concussion-type injury that may be manifested audiometrically as a 4000-Hz dip. Human temporal bone patho­ logy in such cases is similar to that seen in noise-induced hearing loss.27 Similar findings can also be produced by experimental temporal-bone injury.17

LIMITATIONS OF THE AUDIOGRAM We already have noted that an audiogram showing a 4000-Hz dip is not sufficient evidence to make a diagnosis of noise-induced hearing loss. A thorough investigation must be considered to establish the true cause of the hearing loss whenever there is any question regarding etiology. It is not always possible to ascribe a hearing loss to noise or to completely rule out other causes. However, if the patient’s noise exposure has been sufficient, and if investigation fails to reveal other causes of hearing loss, a diag­ nosis of noise-induced hearing loss can be made with reasonable certainty in the presence of supportive audiometric findings.

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Fig. 18.4: Audiogram of a 51-year-old woman who developed sudden hissing tinnitus and a feeling of fullness in her ears during a typical head cold. She had no other ear problems and no noise exposure. The audiogram remained unchanged during a 2-year observation period. — , right; X – – X, left.

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Fig. 18.5: Audiogram of a 24-year-old woman who developed tinni­ tus and a feeling of fulleness in her ears during an attack of herpetic “cold sores” not associated with an upper-respiratory illness. Electronystagmography showed right-sided weakness. Examina­ tion showed decreased sensation in the distribution of the second cervical and glossopharyngeal nerves. — , right; X – – X, left.

Fig. 18.6: Audiogram of a 54-year-old woman who developed bilateral high-pitched tinnitus 2 weeks after beginning an oral diuretic for mild hypertension. Electronystagmography showed nght-sided weakness. Examination showed decrease sensation in the distribution of the second cervical and glossopharyngeal nerves. — , right; X – – X, left.

Hereditary (Genetic) Hearing Loss

Acoustic Neuroma

Hereditary sensorineural hearing loss results commonly in an audiometric pattern similar to that associated with OHL.28–30 This may be particularly difficult to diagnose, because hereditary deafness need not have appeared in a family member previously; in fact, many cases of hereditary hearing loss follow an autosomal recessive inheritance pattern. There have been new developments in identification of genes associated with hereditary hearing loss, making it possible currently to identify specifically some forms of genetic hearing loss.

Eighth-nerve tumors may produce any audiometric pattern, from that of normal hearing to profound deafness, and the 4000-Hz dip is not a rare manifestation of this lesion (Figs. 18.7 and 18.8).31 In these lesions, low speech discrimination scores and patho­logical tone decay need not be present and cannot be relied on to rule out retrocochlear pathology. Nevertheless, asymmetry of hearing loss should arouse suspicion even when a history of noise exposure exists. There are several cases in which patients were exposed to loud noises producing hearing losses that recovered in one ear but not in the other because of underlying acoustic neuromas.

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Ototoxicity The most commonly used ototoxic drugs at present are amino­glycoside antibiotics, diure­tics, chemotherapeutic agents, and aspirin (in high doses).1 When toxic effects are seen, high-frequency sensorineural hearing loss is most common, and profound deafness may result, although a 4000-Hz dip pattern may also be seen (Fig. 18.6).24 Unlike damage caused by the other ototoxic drugs listed above, aspirin-induced hearing loss usually is only temporary, recovering after cessation of the medication.

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Sudden Hearing Loss Each year, clinicians see numerous cases of sudden sensorineural hearing loss of unknown origin. Although the hearing loss is usually unilateral, it may be bilateral; and it may show a 4000-Hz dip. This audiometric pattern may also be seen in patients with sudden hearing loss due to inner-ear membrane breaks32,33 and barotrauma.34,35

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Chapter 18: Occupational Hearing Loss

291

Fig. 18.7: Audiogram of a 28-year-old male machinery worker with a 6-month history of intermittent tinnitus and right-sided hearing loss but without vertigo. Speech discrimination in the right ear was 88%. Electronystagmography showed reduced right-vestibular function. A 1-cm neuroma was removed through the right middle fossa. — , right; X – – X, left. Courtesy of: MD Graham.28

Fig. 18.8: Audiogram of a 40-year-old woman with a 1-year history of tinnitus and right-sided hearing loss that was especially apparent when she used the telephone. Speech discrimination in the right ear was 88%. Electronystagmography revealed absent right caloric responses. A 1.5 cm acoustic neuroma was removed through a translabyrinthine approach. — , right; X – – X, left. Courtesy of: MD Graham.28

Multiple Sclerosis

of sufficient noise exposure. Guidelines for estimating how much noise is necessary to cause hearing loss in most people have been established by the scientific com­munity and the federal government and are reviewed in this chapter. However, a reason­able assessment of a patient’s occupational noise exposure cannot be obtained solely from his/ her history, especially if compensation is a factor. Patients who have worked for many years without hear­ ing protection with weaving looms, papermaking machi­ nes, boilers, sheet metal, riveters, jackhammers, chippers, and the like, nearly always have some degree of OHL. However, many other patients have marked hearing losses that could not possibly have been caused by their minimal exposures to noise. Many patients working in industry can claim that they have been exposed to a great deal of noise. It is essential, especially in compensation cases, to get more accurate information by obtaining from the emp­ loyer, if possible, a written work history and time-weighted average of noise exposure. If a physician does not have first-hand knowledge of the noise exposure in a patient’s job, definitive diagnosis generally should be delayed until such information is made available.

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Multiple sclerosis can also produce sensorineural hearing loss that may show almost any pattern and may fluctuate from severe deafness to normal threshold levels. An example demonstrating a variable 4000-Hz dip is shown in Figure 18.9.

Other Causes A variety of other causes may produce audiograms similar to those seen in noise-induced hearing loss. Such conditions include bacterial infections such as meningitis, systemic toxins,36 and neonatal hypoxia and jaundice. Figure 18.10 illustrates one such sensorineural hearing loss that resulted from kernicterus because of Rh incompatibility.

NOISE EXPOSURE HISTORY It is important to recall that sound of a given frequency spectrum and intensity requires a certain amount of time to produce hearing loss in most subjects. Although the necessary exposure varies from person to person, a diagnosis of noise-induced hearing loss requires a history

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Fig. 18.9: Audiogram of a 20-year-old woman with fluctuating sensorineural hearing loss due to multiple sclerosis. Brainstem evoked-response audiometry showed conduction slowing between the cochlear nucleus and the superior olivary nucleus. — , right; X – – X, left. Courtesy of: MD Graham.28

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Some publications6,9 have perpetuated the idea that exposures to 30 years. After reassessment of available data, the relevant committees of the AAO-HNS, as well as other expert clinicians and the authors of the otolaryngology chapter in the sixth edition of the Guides, have found no credible evidence to support revising the formula again. In addition, the consensus and evidence still indicate that puretone audiometry is the most appropriate test in this population for estimating an individual’s ability to hear speech. While other audiometric tests can be used in the diagnostic process, measures such as discrimination score can be manipulated so easily that they cannot be considered a valid standard for routine determination of hearing performance in medical legal settings. Consequently, the AAO-HNS formula remains the basis for the formula in the AMA Guides. As a result of the exceedingly rigorous scientific process through which the Guides were developed and have evolved, the publication has been recognized and acce­ pted nationally. In nearly all US territories, states, and com­monwealths, the AMA Guides is either recommended or mandated for use by Workers’ Compensation Law. It is also used for actions involving the Federal Employees Compensation Act, Longshore and Harbor Workers’ Compensation Act and Federal Employees Compensation Laws. The AMA Guides to the Evaluation of Impairment is the premier compendium of scientific evidence and expert opinion related to the topic and has been accepted as establishing the standard of care by the American Medical Association and essentially all major specialty societies in the United States (including the AAO-HNS). Physicians involved with patients being assessed for possi­ ble noise-induced or other work-related hearing impairment should be not only loosely familiar with the Guides from past editions, but also current on the latest scientific and methodological advances in the most recent edition of this definitive reference.

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Chapter 18: Occupational Hearing Loss The following is an example of how to calculate hearing impair­ment for compensation purposes (AAO-HNS Guidelines, 1979, and AMA Guides, 2008): 1. The average of the hearing threshold levels at 500, 1000, 2000, and 3000 Hz should be calculated for each ear 2. The percent impairment for each ear should be calculated by multiplying by 1.5% the amount by which the above average hearing threshold level exceeds 25 dB (low fence) up to a maximum of 100%, which is reached at 92 dB (high fence) 3. The hearing handicap, a binaural assessment, should then be calculated by multiplying the smaller percentage (better ear) by 5, adding this figure to the larger percentage (poorer ear), and dividing the total by 6

Example 1. Mild Hearing Loss 500 Hz

1000 Hz

2000 Hz

3000 Hz

Right ear

15

25

45

55

Left ear

20

30

50

60

AAO/Method: 25-dB Fence 1. Right ear: (15 + 25 + 45 + 55)/4 = 140/4 = 35-dB average 2. Left ear: (20 + 30 + 50 + 60)/4 = 160/4 = 40-dB average

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Monaural Impairment: 3. Right Ear: 92–25 = 67 dB × 1.5% = 100.5% (use 100%) 4. Left Ear: 85–25 = 60 dB ×1.5% = 90% 5. Better Ear: 90 × 5 = 450 6. Poorer Ear: 100 × 1 = 100 7. Total: 550÷6 = 91.7% New Jersey method used to calculate the above loss: 1. Right Ear: (80 + 90 +100 +110)/4 = 380/4 = 95 dB (use 92 maximum) 2. Left Ear: [(75 + 80 + 90 + 95)/4] + (340/4) = 85 dB 3. Better ear > 81 dB = 100%

SUMMARY A diagnosis of OHL must be based on specific criteria. Oto­logists rendering medical diagnoses or legal opinions for patients alleging OHL must be careful to base their opinions on facts. The potential medical, legal, and econ­ omic consequences of lesser diligence may be serious. OHL is generally preventable. Ideally, noise should be reduced. When this is not possible, the use of hearing protectors generally provides an effective deterrent to noiseinduced hearing damage. Readers interested in this important, complex topic are encouraged to consult additional sources.1

Monaural impairment:

REFERENCES

3. Right ear: 35–25 = 10 dB × 1.5% = 15% 4. Left ear: 40–25 = 15 dB × 1.5% = 22.5% 5. Better ear: 15 × 5 = 75 6. Poorer ear: 22.5% × 1 = 22.5 7. Total: 97.5 ÷ 6 = 16.25% Model Legislation Method used to calculate the above loss: 1. Right Ear: (15 + 25 + 45 + 55)/4 = 140/4 = 35-dB average 2. Left Ear: (20 + 30 + 50 + 60)/4 = 160/4 = 40-dB average 3. Better ear threshold = 35 dB = 5%

Example 2. Severe Hearing Loss 500 Hz

1000 Hz

2000 Hz

3000 Hz

Right ear

80

90

100

110

Left ear

75

80

90

95

AAO/Method: Average Hearing Test Level 1. Right Ear: (80 + 90 +100 +110)/4 = 95 dB (use 92 maximum) 2. Left Ear: [(75 + 80 + 90 + 95)/4] + (340/4) = 85 dB

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1. Sataloff RT, Sataloff J. Occupational hearing loss, 3rd edn. New York: Taylor & Francis; 2006. 2. Fleming AJ, D’Alonzo CA, Zapp JA. Modern occupational medicine. Philadelphia, PA: Lea & Febiger, 1954. 3. Exploratory Subcommittee Z24-X-2, American Standards Association, The relations of hearing loss to noise exposure, 1954. 4. National Institute for Occupational Safety and Health (NIOSH), Criteria document: Recommendation for an occupational exposure standard for noise, 1972. 5. Baughn WL. Relation between daily noise exposure and hearing loss based on the evaluation of 6,835 industrial noise exposure cases. Wright Patterson AFB OH: Aerospace Medical Research Lab. AMRL-TR-73-53, June 1973. 6. Ward WD, Glorig A. Protocol of inter-industry noise study. J Occup Med. 1975;17:760-70. 7. Burns W, Robinson DS. Hearing and noise in industry. London: Her Majesty’s Stationery Office; 1970. 8. Passchier-Vermeer W. Hearing loss due to steady state broadband noise. Report No. 55, Leiden, The Netherlands: Institute for Public Health, Eng., 1968. 9. Sataloff J, Sataloff RT, Yerg A, et al. Intermittent exposure to noise: Effects on hearing. Ann Otol Rhinol Laryngol. 1983; 92(6):623-8.

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10. Orgler GK, Brownson PJ, Brubaker WW, et al. American Occupational Medicine Association Noise and Hearing Conservation Committee Guidelines for the Conduct of an Occupational Hearing Conservation Program. J Occup Med. 1987;29:981-2. 11. ACOM Noise and Hearing Conservation Committee. Occupational noise-induced hearing loss. J Occup Med. 1989;31:996. 12. On Oct 27, 2002 the American College of Occupational and Environmental Medicine (ACOEM) reaffirmed these criteria in an evidence-based statement which was published in the Journal of Occupational & Environmental Medicine. 2003;45(6):579-81. 13. Kirchner DB, Evenson E, Dobie RA, et al. Occupational Noise-Induced Hearing Loss. ACOEM Task Force on Occupational Hearing Loss. JOEM. 2012;54(1):106-8. 14. Schuknecht HF, Tonndorf J. Acoustic trauma of the cochlea from ear surgery. Laryngoscope. 1960;70:479-505. 15. Lawrence M. Current concepts of the mechanism of occupational hearing loss. Am Ind Hyg Assoc J. 1964; 25:269-73. 16. Kellerhals B. Pathogensis of inner ear lesions in acute acoustic trauma. Acta Otolaryngol. 1972;73:249-53. 17. Schuknecht HG. Pathology of the ear. Cambridge, MA: Harvard University Press; 1974. pp. 295-7, 300-308. 18. Gallo R, Glorig A. Permanent threshold shift changes produced by noise exposure and aging. Am Ind Hyg Assoc J. 1964;25:237-45. 19. Schneider EJ, Mutchler JE, Hoyle HR, et al. The progression of hearing loss from industrial noise exposure. Am Ind Hyg Assoc J. 1970;31:368-76. 20. Sataloff J, Vassallo L, Menduke H. Occupational hearing loss and high frequency thresholds. Arch Environ Health. 1967;14:832-6. 21. Sataloff J, Vassallo L, Menduke H. Hearing loss from exposure to interrupted noise. Arch Environ Health 1969;17: 972-81. 22. Salmivalli A. Acoustic trauma in regular Army personnel: clinical audiologic study. Acta Otolaryngol (Stockh). 1967;(suppl 22):1-85. 23. Ward WD, Fleer RE, Glorig A. Characteristics of hearing losses produced by gunfire and steady noise. J Audiol Res. 1961;1:325-56. 24. Johnsson L-G, Hawkins JE Jr. Degeneration patterns in human ears exposed to noise. Ann Otol Rhinol Laryngol. 1976;85:725-39. 25. Gates GA, Cooper JC Jr, Kannel WB, et al. Hearing in the elderly: the Framingham cohort, 1983–1985. Part I. Basic audiometric test results. Ear Hear. 1990;11(4):247-56. 26. Sataloff J, Vassallo L. Head colds and viral cochleitis. Arch Otolaryngol. 1968;19:56-9. 27. Igarashi M, Schuknecht HF, Myers E. Cochlear pathology in humans with stimulation deafness. J Laryngol Otol. 1964;78:115-23. 28. Anderson H, Wedenberg E. Genetic aspects of hearing impairment in children. Acta Otolaryngol (Stockh). 1970;69:77-88.

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29. Fisch L. The etiology of congenital deafness and audiometric patterns. J Laryngol Otol. 1955;69:479-93. 30. Huizing EH, van Bolhuis AH, Odenthal DW. Studies on progressive hereditary percep­tive deafness in a family of 335 members. Acta Otolaryngol (Stockh). 1966;61:35-41, 161-7. 31. Graham MD. Acoustic tumors: selected histories and patient reviews. In: House WF, Luetje CM (eds), Acoustic tumors. Baltimore, MD: University Park Press; 1979. pp. 192-3. 32. Facer GW, Farell KH, Cody DTR. Spontaneous perilymph fistula. Mayo Clin Proc. 1973;48:203-6. 33. Simmons FB. Theory of membrane breaks in sudden hearing loss. Arch Otolaryngol. 1968;88:67-74. 34. Soss SL. Sensorineural hearing loss with diving. Arch Oto­ laryngol. 1971;93:501-4. 35. Freeman P, Edwards C. Inner ear barotrauma. Arch Oto­ laryngol. 1972;95:556-63. 36. van Dishoeck HAE. Akustisches Trauma. In: Berendes J, Link R, Zollner F (eds), Hals-Nasen-Ohren-Heilkunde. Band III. Stuttgart: Georg Thieme; 1966. pp. 1764-99. 37. Yerg RA, Sataloff J, Glorig A, et al. Inter-industry noise study. J Occup Med. 1978;20:351-8. 38. Cartwright LB, Thompson RW. The effects of broadband noise on the cardiovascular system in normal resting adults. Am Ind Hyg Assoc J. 1978:653-8. 39. Johnsson L-G, Hawkins JE Jr. Strial atrophy in clinical and experimental deafness. Laryngoscope. 1972;82:1105-25. 40. Spoendlin H. Histopathology of nerve deafness. J Oto­ laryngol. 1985;14(5):282-6. 41. Spoendlin H, Brun JP. Relation of structural damage to exposure time and intensity in acoustic trauma. Acta Oto­ laryngol. 1973;75:220-26. 42. Spoendlin H. Primary structural changes in the organ of Corti after acoustic over-stimulation. Acta Otolaryngol. 1971;71:166-76. 43. Carson SS, Prazma J, Pulver SH, et al. Combined effects of aspirin and noise in causing permanent hearing loss. Arch Otolaryngol Head Neck Surg. 1989;115:1070-75. 44. Barone JA, Peters JM, Garabrant DH, et al. Smoking as a risk factor in noise-induced hearing loss. J Occup Med. 1987;29(9):741-6. 45. Thomas GB, Williams CE, Hoger NG. Some non-auditory correlates of the hearing threshold levels of an aviation noise exposed population. Aviat Spac Environ Med. 1981; 9:531-6. 46. Chung DY, Wilson GN, Gannon RP, et al. Individual susceptibility to noise. In: Hamernik RP, Henderson D, Salvi R (eds), New perspectives in noise-induced hearing loss. New York: Raven Press; 1982. pp. 511-19. 47. Drettner B, Hedstrand H, Klockhoff I, et al. Cardiovascular risk factors and hearing loss. Acta Otolaryngol. 1975;79: 366-71. 48. Siegelaub AB, Friedman GD, Adour K, et al. Hearing loss in adults. Arch Environ Health. 1984;29:107-9. 49. Cocchiarella LA, Sharp DS, Persky VW. Hearing threshold shifts, white-cell count and smoking status in working men. Occup Med (Lond). 1995;45:179-85.

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Chapter 18: Occupational Hearing Loss 50. Starck J, Toppila E, Pyykko I. Smoking as a risk factor in sensory neural hearing loss among workers exposed to occupational noise. Acta Otolaryngol (Stockh). 1999;119:302-5. 51. Sulkowski WJ, Kowalska S, Matyja W, et al. Effects of occupational exposure to a mixture of solvents on the inner ear: a field study. Int J Occup Med Environ Health. 2002;15: 247-56. 52. Sliwinska-Kowalska M, Zamyslowska-Szmytke E, Szymczak W, et al. Ototoxic effects of occupational exposure to styrene and co-exposure to styrene and noise. J Occup Environ Med. 2003;45:15-24. 53. Sataloff RT, Davies B, Myers DL. Acoustic neuromas presenting as sudden deafness. Am J Otol. 1985;6(4):349-52. 54. American Medical Association. Guides to the Evaluation of Permanent Impairment, 6th edn. Chicago, IL: American Medical Association; 2008. 55. Sataloff RT. Evaluating occupational hearing loss: the value of the AMA guides to the evaluation of permanent impairment [editorial]. ENT J. 2014;93(4-5):132-5. 56. American Medical Association. A guide to the evaluation of permanent impairment of the extremities and back. JAMA. 1958;166(suppl):1-122. 57. Guides to the Evaluation of Permanent Impairment. Chicago, IL: American Medical Association; 1971. 58. World Health Organization. International Classification of Functioning, Disability and Health: ICF. Geneva, Switzerland: World Health Organization; 2001. 59. Resolution of the World Health Organization. International classification of functioning, disability and health. 54th World Health Assembly; May 22, 2001.

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60. Guide for the evaluation of hearing impairment. J Occup Med. 1959;1(3):167-8. 61. American Academy of Otolaryngology Committee on Hear­ ing and Equilibrium and American Council of Otolaryn­ gology Committee on the Medical Aspects of Noise. Guide for the evaluation of hearing handicap. JAMA. 1979;241: 2055-59. 62. Dobie RA, Sakai CS. Monetary compensation for hearing loss: clinician survey. JOHL. 1998;1(1):73-80. 63. Doerfler LG, Nett EM, Matthews J. The relationships between audiologic measures and handicap: Part One. JOHL. 1998;1(2):103-52. 64. Dobie RA, Sakai CS. Monetary compensation for hearing loss: choice and weighting of frequencies. 1998;1(3): 163-71. 65. Doerfler LG, Nett EM, Matthews J. The relationships between audiologic measures and handicap: part two. JOHL. 1998;1(3):213-35. 66. Sataloff J, Vassallo LA, Sataloff RT. The validity of the AMA impairment formula for hearing loss. JOHL. 1998;1(4): 237-42. 67. Doerfler LG, Nett EM, Matthews J. The relationships between audiologic measures and handicap: part 3. JOHL. 1998;1(4):243-64. 68. Nelson RA. Development of the AMA formula or who built this camel anyway? JOHL. 1999;2(4):145-51. 69. American Speech-Language-Hearing Association. Task Force on the Definition of Hearing Handicap. http://www. asha.org/docs/html/RP1981-00022.html. Accessed August 7, 2012.

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CHAPTER

19

Ototoxicity Karen Jo Doyle, Brent Wilkerson

INTRODUCTION/BACKGROUND This chapter covers the major classes of pharmaceutical drugs that have been demonstrated to produce hearing loss and/or vestibular loss. Some classes of ototoxic drugs such as salicylates, aminoglycosides, and platinum chemo­therapy drugs have been known to produce adverse effects on their inner ear since their discovery but con­ tinue to be used because in many clinical settings their efficacy outweighs their potential for toxicity. In other cases, such as the combination of opioid analgesic Vico­ din, macrolide antibiotics erythromycin, clarithromycin and azithromycin, the chemotherapy/chemoprevention agent α-difluoromethylornithine (DFMO), and the oral chemotherapy drug imatinib (Gleevec), the drugs were placed into use before their ototoxicities were recognized. More than a century ago, aspirin was the first drug found to produce hearing loss.1 In the 1940s reversible hearing loss and tinnitus were observed in patients treat­ ed with large doses of aspirin.2–3 McCabe and Dey studied the effects of 925 mg of aspirin given four times daily for 5 days to volunteers, finding that it produced tinnitus and hearing loss (worse for high frequencies) that increased in severity each day, but were completely reversible within 72 hours of stopping its administration.4 In similar experi­ ments, Meyers et al. noted that when aspirin was taken by patients with rheumatoid arthritis at doses as high as 6–8 g per day, the hearing loss was flat across frequencies and reached severity of as much as 40–50 dBHL.5 Again, the hearing loss was completely reversible after discon­ tinuing the drug. These same authors administered high doses of aspirin subcutaneously to squirrels and found no

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histological abnormalities in the cochlea despite noting 30 dB hearing loss in the animals.6 The earliest aminoglycoside antibiotic, streptomycin, was discovered by Schatz in 19437 and was used to treat tuberculosis in the first ever randomized clinical trial of a drug.8 Soon after its introduction streptomycin was docu­ mented to cause permanent hearing loss in tuberculosis patients.9 Other aminoglycoside antibiotics—neomycin, kanamycin, and gentamicin—were introduced in 1949, 1956, and 1963.10–12 Unfortunately, all aminoglycoside anti­ biotics demonstrated ototoxic effects. In 1966, furosemide was the first loop diuretic used in the United States. However, the first report of loop diuretic ototoxicity was in 1965 by Maher and Schreiner, who demonstrated reversible hearing loss in patients with clin­ ical edema treated using ethacrynic acid.13 Similar ototoxic effects were later noted for furosemide.14 Permanent hear­ing loss occurred when loop diuretics were given in patients having renal failure.15 The platinum chemotherapy drugs cisplatin, carbo­ platin, and oxaliplatin are used to treat a large variety of cancers. Cisplatin received full FDA approval in 1978, after the first clinical trial was published in 1972.16 Early reports acknowledged cisplatin’s adverse effects on hear­ ing, but given its chemotherapeutic efficacy the side effect was underemphasized.17

PATHOGENESIS Ototoxic drugs have their effects on different parts of the auditory/vestibular system. The peripheral auditory sys­ tem (Fig. 19.1) consists of the outer ear, the middle ear,

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Fig. 19.1: Peripheral auditory system.

the cochlea and auditory nerve, while the central auditory system (Fig. 19.2) consists of brainstem and cortical neural pathways that convey neural signals. The human periph­ eral vestibular system includes the inner ear structures (in each ear the utricle, saccule and three semicircular canals), vestibular nerves, and central peripheral path­ ways. An ototoxic medication can have effects on one or more of these components. There has been much inves­ tigation of the mechanisms by which different classes of ototoxic drugs produce sensorineural hearing loss.

Mechanisms of Aminoglycoside Ototoxicity In aminoglycoside toxicity, aminoglycosides enter hair cells through mechanically sensitive ion channels on the tips of the stereocilia of hair cells.18 Figures 19.3A and B show the molecular structure of gentamicin and strepto­ mycin. Aminoglycosides produce their ototoxic effects by generation of free radicals within the inner ear, inducing apoptosis of outer hair cells in the cochlea19,20 and type 1 hair cells in the vestibular system.21 Research that demons­ trates how depletion of free radicals by antioxidants such as glutathione, iron, methionine, and superoxide dis­ mutase reduces aminoglycoside ototoxicity supports this mechanism.22

Mechanisms of Cisplatin Ototoxicity As in aminoglycoside ototoxicity, with cisplatin adminis­ tration oxygen radicals are generated, followed by outer hair cell apoptosis.23,24 The molecular structure of the platinum chemotherapy agents cisplatin, carboplatin, and oxaliplatin is shown in Figure 19.4. Outer hair cell loss

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Fig. 19.2: Central auditory system.

happens first in the basal cochlea and proceeds apically as damage increases.25 Damage to supporting cells in the organ of Corti26 and atrophy of the stria vascularis27 have been reported with cisplatin. Unlike the aminoglycosides, the platinum chemotherapy agents cause little altera­ tion in the peripheral vestibular system. Pretreatment of experi­mental animals with the antioxidant D-methionine can prevent some of the loss of inner hair cells that is unique to carboplatin ototoxicity.28

Mechanisms of Salicylate Ototoxicity Aspirin ototoxicity is completely reversible and does not cause gross histopathological changes.6 Stypulchowski described the effects of salicylates on cochlear potentials in the cat, noting that they decreased the amplitudes of the action potential and summating potential, while increas­ ing the amplitude of the cochlear microphonic.29 Simi­ larly, salicylates can increase levels of distortion product otoacoustic emissions.30 However, others have shown that salicylates diminish outer hair cell electromotility and spontaneous otoacoustic emissions.31–33 Salicylates decrease outer hair cell wall stiffness and motility.34,35

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A

309

B

Figs. 19.3A and B: Chemical structures of gentamicin and streptomycin.

Fig. 19.4: Molecular structures of cisplatin, carboplatin, and oxali­ platin.

Fig. 19.5: Structure of the aspirin molecule.

Figure 19.5 shows aspirin’s molecular structure. Others have found evidence that salicylate directly and rever­ sibly inhibits chloride anions at the anion-binding site of prestin, the motor molecule of the outer hair cells.36 Still others have produced evidence that salicylate blocks the outer hair cell potassium channel KCNQ4 as an alternate mechanism of salicylate ototoxicity.37 Salicylate has mul­ tiple effects in the central nervous system, and is believed to enhance sound-evoked central auditory activity.38

inhibited by the loop diuretics39 (Fig. 19.6). In animals, administration of loop diuretics reduces the endocochlear potential, which is reversible. The hearing loss produced by loop diuretics is typically reversible in animals.40

Mechanisms of Loop Diuretic Ototoxicity Na-K-2Cl cotransporter is also found at the basal plasma membrane of marginal cells of the stria vascularis and is

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Mechanisms of DFMO Ototoxicity DFMO is an irreversible blocker of the enzyme ornithine decarboxylase, the first step in the synthesis of polya­ mines.41 The polyamines putrescine, spermidine, and sper­ mine are positively charged molecules that are found in nearly every cell (Fig. 19.7).42 Very-high-dose oral adminis­ tration of DFMO causes some hair cell damage in animal models.43 However, there are no gross histopathological

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Fig. 19.7: DFMO blocks the enzyme ODC and therefore polyam­ ine synthesis. (DFMO, α-difluoromethylornithine).

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changes in the cochlea when DFMO is given at lower doses subcutaneously for a month in the gerbil, even though mild hearing loss affecting all frequencies tested occurred that was completely reversible after 3 weeks of recovery.44 Administration of DFMO lowers the endocochlear poten­ tial.45 The intermediate cells of the stria vascularis contain inwardly rectifying K+ channels (Kir4.1), and similar chan­ nels that are found in other tissues such as the heart owe their inward rectification properties to voltage dependent blockage of these channels by the positively charged polyamines.46,47 Nie et al. concluded that the reversible hearing loss following administration of DFMO to mice is produced by alteration of intermediate cell Kir4.1 channel inward rectification.45

Mechanisms of Hydrocodone/ Acetaminophen Ototoxicity

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When taken at much higher than recommended doses, the commonly prescribed combination analgesic hydrocodone and acetaminophen (Vicodin) causes a rapidly progres­ sive and irreversible sensorineural deafness.48–50 There is only one investigation of the possible mechanism of high dose Vicodin. Neonatal mouse cultures and auditory cell lines were exposed in vitro to different concentrations of

Mechanisms of Macrolide Ototoxicity Despite numerous clinical reports of hearing loss due to erythromycin and the other macrolide antibiotics, there are no journal articles relevant to pathophysiology. Brummett et al. published an abstract reporting that when erythromycin was infused intravenously in guinea pigs, initially there was an increase in the latency of the fourth wave of the auditory brainstem response.52 Eventually, the fourth wave disappeared, followed by the third and the second waves. All peaks returned when the drug was discontinued, and there was no change in the action potential. They concluded that erythromycin had a central auditory system site of ototoxic action.

Vinka Alkaloid Mechanisms of Ototoxicity There are very few cases of ototoxicity related to the use of vincristine and vinblastine, anti cancer drugs derived from the periwinkle plant, Vinca rosea.53–56 Serafy and -

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Fig. 19.6: NKCC1 co transporter on the basal membrane of the marginal cell.

acetaminophen alone, hydromorphone (metabolite of hydrocodone) and the combination of the two.51 Aceta­ minophen exposure caused cell death that was further potentiated when combined with hydromorphone, while exposure to hydrocodone or hydromorphone alone failed to kill cells. They concluded that acetaminophen was the more likely cause of Vicodin ototoxicity, though the com­ bination was more damaging.

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Chapter 19: Ototoxicity colleagues published the only animal studies relevant to vinca alkaloid ototoxicity.57–58 They found that vinblas­ tine damaged organ of Corti hair cells in rabbits, while vincristine destroyed hair cells as well as spiral ganglion cells.

CLINICAL FINDINGS IN OTOTOXICITY Aminoglycosides Aminoglycoside ototoxicity can be identified in one third of treated patients who undergo audiological screening.59 It manifests as a permanent high-frequency sensorineural hearing loss that progresses from higher frequencies to lower frequencies and is related to the number of doses of drug.60 Some authors have reported that streptomycin is the most cochleotoxic aminoglycoside, while others have found gentamicin to be more cochleotoxic, though kana­ mycin and neomycin are usually thought to be the most cochleotoxic aminoglycosides.61 Kanamycin and amikacin are primarily cochleotoxic, while streptomycin and gen­ tamicin have greater vestibulotoxicity.62 Genetic predis­ position to aminoglycoside ototoxicity via mitochondrial DNA mutations has been discovered due to mutations in mitochondrial 12S ribosomal rRNA.63 Because amino­ glycosides initially produce a relatively asymptomatic high-frequency sensorineural hearing loss and because the incidence of hearing loss is unrelated to serum an­ tibiotic levels, some authors have proposed screening high-frequency audiometric thresholds during treatment periods to identify ototoxicity before it becomes severe.64

Cisplatin Cis-platinum is the most ototoxic drug in that it causes irreversible high-frequency sensorineural hearing loss in approximately 70% of patients receiving it, which is dependent upon cumulative dose of the drug.65 Tinnitus typically precedes the hearing loss, and the hearing loss first involves the high frequencies but can progress to low­ er frequencies as therapy continues. Risk factors include young or advanced age, renal insufficiency, coadministra­ tion of high-dose vincristine, and cranial irradiation. Chil­ dren under the age of 5 years are particularly susceptible to cisplatin ototoxicity, having a 40% incidence of hearing loss.66 Patients with both alleles of Val-GSTP1 may have more glutathione available to protect against cisplatin and are less likely to have the ototoxic hearing loss.67 Vestibulo­ toxicity does not typically occur with platinum agents.

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Salicylates Hearing loss due to large doses of salicylates may involve the high frequencies but is usually flat across frequencies, mild to moderate, and reversible after discontinuance of the drug.4,5 Increasing dosage and duration produces a greater degree of hearing loss for the frequencies 250–8000 Hz.68

Loop Diuretics In humans, every loop diuretic except torsemide has been reported to cause hearing loss, both temporary and per­ manent. The patients have usually suffered from renal failure and underwent rapid infusion of the diuretic.69 The hearing loss is often reversible and is typically mild, affecting the middle frequency range.70–72 Edema of the stria vascularis was found in temporal bone histopatho­ logy of patients after loop diuretic ototoxic hearing loss.73,74

Macrolide Antibiotics Erythromycin ototoxicity is reported to present as relative­ ly mild sensorineural hearing loss, flat across frequencies, appearing within days of high-dose intravenous adminis­ tration, and usually reversible.75,76 There are, however, indi­ vidual case reports of irreversible macrolide ototoxicity.77

DFMO At high doses (>1 g/m2), DFMO causes hearing loss from 250 to 8000 Hz that is often reversible.78 At low doses used for chemoprevention, DFMO produces at worst a minimal hearing loss that is always reversible.79,80 Unlike salicylate ototoxicity, the hearing loss from DFMO reverses slowly, over days to months.79

Vicodin The patients described in case reports of Vicodin oto­ toxicity had rapidly progressive, permanent sensorineural deafness. Fortunately, the patients benefited from cochle­ ar implantation.44–46 The audiograms presented showed involvement across frequencies, and the patients had no vestibular complaints.46

Imatinib (Gleevec) Imatinib is an oral tyrosine kinase inhibitor used initially to treat chronic myelogenous leukemia that is FDA-approved to treat myelodysplastic diseases, lymphoma as well as

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Vincristine/Vinblastine Only a few cases of vinblastine or vincristine ototoxicity have been reported, two of which were at least partially reversible.53–56

PREVENTION OF OTOTOXICITY

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CONCLUSION In this chapter, we have reviewed the classes of pharma­ ceutical agents known to confer varying degrees of revers­ ible or permanent hearing loss or vestibular damage in humans. New compounds are constantly being intro­ duced, as well as biological agents for treatment of can­ cers and inflammatory diseases, some of which may be ototoxic.91 Clinicians should acquaint themselves with these adverse side effects, and scientists should investigate these agents to identify ways to cure or prevent ototoxicity, and to discover more about the workings of the auditory system.

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Because both aminoglycoside and platinum chemothe­ rapy drugs seem to generate reactive oxygen species in the cochlea that lead to killing of outer hair cells via caspase dependent or caspase independent cell death mecha­ nisms, a great deal of work has been dedicated to preventing toxicity by administration of antioxidants or chelators to decrease reactive oxygen species.62 Several antioxidant sulfur containing compounds (methionine, lipoic acid, N acetylcysteine, and amifostine) have been shown in animals to protect from cisplatin ototoxicity; their applica­ tion in human trials is still uncertain because of concerns that these compounds may interfere with the tumoricidal effects of the platinum drugs.84 One clinical trial has been performed in China, showing that administration of aspi­ rin, an iron chelator and free radical scavenger, reduces gentamicin ototoxicity from 13% to 3%.85 Other authors have proposed protection of hair cells by inoculating an adenoviral vector encoding human neurotrophic factor.86 In vivo inoculation of adenovirus with the Math1 gene inserted into guinea pig cochlear endolymph results in Math1 overexpression in the organ of Corti , new hair cells, and axons extended from the auditory nerve bundle toward the new hair cells.87 In aminoglycoside treated mice, delivery of Math1 via adenovirus vector induced recovery of the vestibular neuroepithelium within 8 weeks after treatment.88

Another method proposed to prevent ototoxic hair cell damage is to prevent the aminoglycoside molecule from entering the hair cell through the mechano electri­ cal transducer channels.89 Huth et al. point out that one could modify the chemical structure of aminoglycosides to widen their diameters by binding inert molecules on sites irrelevant for antimicrobial activity to prevent passage of aminoglycoside molecules through the channel into the hair cells, while ensuring that the molecules could still pass into the bacterial ribosome.90

other tumors. Only three case reports have linked imatinib to progressive sensorineural hearing loss, irreversible in all cases, moderately severe to severe, and flat across frequencies in two of the three patients, with poor word discrimination (one patient did not undergo audiological evaluation).81–83 The author of this chapter recently saw a 6 year old child treated for 8 months with oral imatinib for non Hodgkin's lymphoma who developed profound deafness during the course of treatment (unpublished observation). The mechanism for the hearing loss associ­ ated with Gleevec has not been studied, though tyrosine kinases are present in mammalian auditory neurons and could be the ototoxic target.83

1. Muller G. Beitrag zur wirking der salicylasuren natrons beim diabetes melleus. Berl Klink Wochenschrift. 1877;14:29 31. 2. Jager BV, Alway R. The treatment of acute rheumatic fever with large doses of sodium salicylate; with special refer­ ence to dose management and toxic manifestations. Am J Med Sci. 1946;211:273 85. 3. Graham JD, Parker WA. The toxic manifestations of sodium salicylate therapy. Q J Med. 1948; 17:153 63. 4. McCabe PA, Dey FL. The effect of aspirin upon auditory sensitivity. Ann Otol Rhinol Laryngol. 1965;74:213 25. 5. Meyers E, Bernstein J, Fostiropolous G. Salicylate ototoxic­ ity: a clinical study. N Engl J Med. 1965;273:587 90. 6. Meyers EN, Bernstein JM. Salicylate ototoxicity. Arch Oto­ larygol. 1965;82:483 93. 7. Schatz A, Bugie E, Waksman SA. Streptomycin: a sub­ stance exhibiting antibiotic activity against gram positive and gram negative bacteria. Proc Soc Exper Bio Med. 1944; 55:66 9. 8. Medical Research Council. Streptomycin treatment of pulmonary tuberculosis: A Medical Research Council Investigation. Br Med J. 1948;2:769 82. 9. Hinshaw HC, Feldman WH. Streptomycin in the treatment of clinical tuberculosis: a preliminary report. Proc Mayo Clin. 1945;20:313 18.

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Chapter 19: Ototoxicity 10. Waksman SA, Lechevalier HA. Neomycin a new antibiotic active against streptomycin-resistant bacteria, including tuberculosis organisms. Science. 1949;109:305-7. 11. Umezawa H, Ueda M, Maeda K, et al. Production and iso­ lation of a new antibiotic: kanamycin. J Antibiotics. 1957; 10:181-8. 12. Weinstein MJ, Luedemann E, Oden EM, et al. Gentamicin, a new antibiotic complex from Micromonospora. J Medicinal Chem. 1963;6:463-4. 13. Maher JF, Schreiner GE. Studies on ethacrynic acid in patients with refractory edema. Ann Intern Med. 1965;62: 15-29. 14. Schwartz GN, David DS, Riggo RR, et al. Ototoxicity induced by furosemide. N Eng J Med. 1970;181:1413-4. 15. Pillay VKG, Schwartz FD, Aimi K, et al. Transient and per­ manent deafness following treatment with ethacrynic acid in renal failure. Lanet. 1969;1:77-9. 16. Rossof AH, Slayton ER, Perlia CP. Preliminary clinical expe­ rience with cis-diamminedichloroplatinum. Cancer. 1972; 30:1451-6. 17. Kovach JS, Moertel CG, Schutt AJ, et al. Phase II study of cis-diamminedichloroplatinum in advanced carcinoma of the large bowel. Cancer Chemother Rep. 1973;57:357-9. 18. Vu AA, Nadaraja GS, Huth ME, et al. Integrity and regen­ eration of mechanotransduction machinery regulate ami­ noglycoside entry and sensory cell death. PLoS One. 2013; e54794. 19. Clerici WJ, Hensley K, DiMartino DL, et al. Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res. 1996;98:116-24. 20. Hirose K, Hockenberry DM, Rubel EW. Reactive oxygen species in chick hair cells after gentamicin exposure in vitro. Hear Res. 1997;104:1-14. 21. Hawkins JE. Drug ototoxicity. In: WD Keidel, WD Neff (eds), Handbook of sensory physiology. Berlin: Springer Verlag; 1976, pp. 707-48. 22. Song BB, Schact J. Variable efficacy of radical scavengers and iron chelators to attenuate gentamicin ototoxicity in guinea pig in vivo. Hear Res. 1996;94:87-93. 23. Ravi R, Somani SM, Rybak LP. Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol. 1995; 76:386-94. 24. Rybak LP, Whitworth C, Somani S. Application of anti­ oxidants and other agents to prevent cisplatin ototoxicity. Laryngoscope. 1999;109:1740-44. 25. Schweitzer VG, Hawkins JE, Lilly DJ, et al. Ototoxic and nephrotoxic effects of combined treatment with cis-diam­ minedichloroplatinum and kanamycin in the guinea pig. Otolaryngol Head Neck Surg. 1984;92:38-49. 26. Ramirez-Camacho R, Garcia-Berrocal JR, et al. Supporting cells as a target of cisplatin-induced inner ear damage: therapeutic implications. Laryngoscope. 2004;114:533-7. 27. Meech RP, Campbell KC, Hughes LP, et al. A semiquan­ titative analysis of the effects of cisplatin on the rat stria vascularis. Hear Res. 1998;124:44-59.

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28. Lockwood DS, Ding DL, Wang J, et al. D-methionine atten­ uates inner hair cell loss in carboplatin-treated chinchillas. Audiol Neurotol. 2000;5:263-6. 29. Stypulkowski PH. Mechanisms of salicylate ototoxicity. Hear Res. 1990;46:113-45. 30. Huang ZW, Luo Y, Wu Z, et al. Paradoxical enhancement of active cochlear mechanics in long-term administration of salicylate. J Neurophysiol. 2005;93:2053-61. 31. Shehata WE, Brownell WE, Dieler R. Effects of salicylate on shape electromotility and membrane characteristics of isolated outer hair cells from guinea pig cochlea. Acta Otolaryngol. 1991;111:707-18. 32. Wier CC, Pasanen EG, McFadden D. Partial dissociation of spontaneous otoacoustic emissions and distortion prod­ ucts during aspirin use in humans. J Acoust Soc Am. 1988; 84:230-37. 33. Long GR, Tubis A. Modification of spontaneous and evoked otoacoustic emissions and associated psycho­ acoustic microstructure by aspirin consumption. J Acoust Soc Am. 1988;84:1343-53. 34. Lue AJ, Brownell WE. Salicylate induced changes in outer hair cell lateral wall stiffness. Hear Res. 1999;135:163-8. 35. Dieler R, Shehata-Dieler WE, Brownwell WE. Concomitant salicylate-induced alterations of outer hair cell subsurface cisternae and electromotility. J Neurocytol. 1991;20:637-53. 36. Rybalchenko V, Santos-Sacchi J. Cl– flux through a nonselective, stretch-sensitive conductance influences the outer hair cell motor of the guinea-pig. J Physiol. 2003;547: 873-91. 37. Wu T, Lv P, Kim HJ, et al. Effect of salicylate on KCNQ4 of the guinea pig outer hair cell. J Neurophysiol. 2010;103: 1969-77. 38. Chen GD, Stolzberg D, Lobarinas E, et al. Salicylateinduced cochlear impairments, cortical hyperactivity and re-tuning, and tinnitus. Hear Res. 2013;295:100-13. 39. Wangemann P, Liu J, Marcus DC. Ion transport mecha­ nisms responsible for K+ secretion and the transepithelial voltage across marginal cells of the stria vascularis in vitro. Hear Res. 1995;84:19-29. 40. Rybak LP, Whitworth C, Scott V. Comparative acute oto­ toxicity of loop diuretic compounds. Eur Arch Oto-RhinoLaryngol. 1991;101:1167-74. 41. Sjoerdsma A, Schechter J. Chemotherapeutic implications of polyamine biosynthesis inhibition. Clin Pharmacol Ther. 1984;35:287-300. 42. Tabor CW, Tabor H. Polyamines. Ann Rev Biochem. 1984; 53:749-90. 43. Salzer SJ, Mattox DE, Brownell WE. Cochlear damage and increased threshold in alpha-difluoromethylornithine (DFMO) treated guinea pigs. Hear Res. 1990;46:101-12. 44. Smith MC, Tinling S, Doyle KJ. Difluoromethylornithineinduced reversible hearing loss across a wide frequency range. Laryngoscope. 2004;114:1113-7. 45. Nie L, Feng W, Diaz R, et al. Functional consequences of poly­ amine synthesis inhibition by α-difluoromethylornithine (DFMO). J Biol Chem. 2005;280:15097-102.

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66. Li Y, Womer RB, Silber JH. Predicting cisplatin ototoxicity in children: the influence of age and the cumulative dose. Eur J Cancer. 2004;40:2445 51. 67. Oldenburg J, Kraggerud SM, Cvancarova M, et al. Cisplatin induced long term hearing impairment is associated with specific glutathione S transferase genotypes in testicular cancer survivors. J Clin Oncol. 2007;25:708 14. 68. McFadden D, Plattsmier H. Aspirin can potentiate the tem­ porary hearing loss induced by intense sounds. Hear Res. 1983;9:295 316. 69. Wigand MD, Heidland A. Ototoxic side effects of high doses of furosemide in patients with uremia. Postgrad Med J. 1971;47(Suppl):54 6. 70. Heidland H, Wigand ME. The effect of furosemide at high doses on auditory sensitivity in patients with uremia. Klin Wochenschr. 1970;48:1051 6. 71. Boston Collaborative Drug Surveillance Program. Drug induced deafness: a cooperative study. JAMA. 1973;224: 516 7. 72. Tuzel IH. Comparison of adverse reactions to bumetanide and furosemide. J Clin Pharmacol. 1981;21:615 9. 73. Matz GJ. The ototoxic effects of ethacrynic acid in man and animals. Laryngoscope. 1976;86:1065 86. 74. Arnold W, Nadol JB, Geidauer H. Ultrastructural histopa­ thology in a case of human ototoxicity due to loop diuretics Acta Otolaryngol. 1981;91:391 414. 75. Mintz U, Amir J, Pinkhas J, et al. Transient perceptive deaf­ ness due to erythromycin lactobionate. J Am Med Assn. 1973; 226: 1122 3. 76. McGhan LJ, Merchant SN. Erythromycin ototoxicity. Otol Neurotol. 2003; 24: 701 2. 77. Coulston J, Balaratnam N. Irreversible sensorineural hear­ ing loss due to clarithromycin. Postgrad Med J. 2005; 81: 58 9. 78. Croghan MK, Aickin MG, Meyskens FL. Dose related alpha difluoromethylornithine ototoxicity. Am J Clin Oncol. 1991; 14:331 5. 79. Pasic TR, Heisey D, Love RR, α difluoromethylornithine. J Natl Cancer Inst. 1993;85:732 6. 80. Meyskens FL, Gerner EW, Emerson S, et al. Effect of α difluoromethylornithine on rectal mucosal levels of polyamines in a randomized, double blinded trial for colon cancer prevention. J Natl Cancer Inst. 1998;90:1212 8. 81. Attili VSS, Bapsy PP, Anupama G, et al. Irreversible sen­ sorineural hearing loss due to Imatinib. Leuk Res. 2008; 32: 991 2. 82. Janssen JJWM, Berendse HW, Schuurhuis GJ, et al. A 51 year old male CML patient with progressive hearing loss, confusion, ataxia, and aphasia during imatinib treat­ ment. Am J Hematol. 2009;84:679 82. 83. Lin HE, Roberts DS, Kay J, et al. Sensorineural hearing loss following Imatinib (Gleevec) administration. Otolaryngol Head Neck Surg. 2012;146:335 7. 84. Rybak LP, Whitworth CA. Ototoxicity: therapeutic oppor­ tunities. Drug Discovery Today. 2005;10:1313 21. 85. Chen Y, Huang WG, Zha DJ, et al. Aspirin attenuates gen­ tamicin ototoxicity: From the laboratory to the clinic. Hear Res. 2007;226:178 82.

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46. Hibino H, Horio Y, Inanobe A, et al. An ATP dependent inwardly rectifying potassium channel, KAB 2 (Kir4.1), in cochlear stria vascularis of inner ear: Its specific subcel­ lular localization and correlation with the formation of endocochlear potential. J Neurosci. 1997;17:4711 21. 47. Lopatin AN, Nichols CG. [K+] dependence of polyamine induced rectification in inward rectifier potassium chan­ nels (IRK1, Kir2.1). J Gen Physiol. 1996;108:105 13. 48. Friedman RA, House JW, Luxford WM, et al. Profound hearing loss associated with hydrocodone/acetaminophen abuse. Am J Otol. 2000;21:188 91. 49. Oh AK, Ishiyama A, Baloh RW. Deafness associated with abuse of hydrocodone/acetaminophen. Neurology. 2000; 54:2345. 50. Ho T, Vrabec JT, Burton AW. Hydrocodone use and senso­ rineural hearing loss. Pain Physician. 2007;10:467 72. 51. Yorgason JG, Kalinec GM, Luxford WM, et al. Acetamino­ phen ototoxicity after acetaminophen/hydrocodone abuse: evidence from two parallel in vitro mouse models. Oto­ laryngol Head Neck Surg. 2010;142:814 9. 52. Brummett RE, Hager G, Fox KE, et al. Association for Research in Otolaryngology Midwinter Meeting Abstracts. 1984;36:25. 53. Moss PE, Hickman S, Harrison BR. Ototoxicity associated with vinblastine. Ann Pharmacother. 1997;33:423 5. 54. Lugassy G, Shapira A. Sensorineural hearing loss associ­ ated with vincristine treatment. Blut 1990;61(5):320 21. 55. Mahajan SL. Acute acoustic nerve palsy associated with vincristine therapy. Cancer. 1981;24:2404. 56. Yousif H, Richardson SG, Saunders W. Partially reversible nerve deafness due to vincristine. Postgrad Med J. 1990;66: 688 9. 57. Serafy A, Hashash M, State F. The effect of vinblastine sul­ fate on the neurological elements of the rabbit cochlea. J Laryngol Otol. 1982;96:975 9. 58. Serafy A, Hashash M. The effect of vincristine on the neu­ rological elements of the rabbit cochlear. J Laryngol Otol. 1981;95:49 54. 59. Fausti SA, Henry JA, Helt WJ, et al. An individualized, sen­ sitive frequency range for early detection of ototoxicity. Ear Hear. 1999;20:497 505. 60. Mulheran M, Degg C, Burr S, et al. Occurrence and risk of cochleotoxicity in cystic fibrosis patients receiving repeated high dose aminoglycoside therapy. Antimicrob Agents Chemother. 2001;45:2502 9. 61. Kalkandelen S, Selimoglu E, Ergogan F, et al. Comparative cochlear toxicities of streptomycin, gentamicin, amika­ cin and netilmicin in guinea pigs. J Int Med Res. 2002;30: 406 12. 62. Rybak LP, Ramkumar V. Ototoxicity. Kidney Int. 2007;72: 931 5. 63. Fischel Ghodsian N. Genetic factors in aminoglycoside toxicity. Ann N Y Acad Sci. 1999;884:99 109. 64. Fausti SA, Henry J, Schaffer HI, et al. High frequency audiometric monitoring for early detection of aminogly­ coside ototoxicity. J Infect Dis. 1992;165:1026 32. 65. Wright CG, Schaefer SD. Inner ear histopathology in patients treated with cis platinum. Laryngoscope. 1982;92:1408 13.



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Chapter 19: Ototoxicity 86. Yagi M, Magal E, Sheng Z, et al. Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated over­ expression of glial cell line-derived neurotrophic factor. Human Gene Ther. 1999;10:813-23. 87. Kawamoto K, Ishimoto S, Minoda R, et al. Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo. J Neurosci. 2003;23:4395-400. 88. Staeker H, Praetorius M, Baker K, et al. Vestibular hair cell regeneration and restoration of balance function indu­ ced by math1 gene transfer. Otology Neurotol. 2007;28: 223-31.

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89. Marcotti W, van Netten SM, Kros CJ. The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer chan­ nels. J Physiol. 2005;567:505-21. 90. Huth ME, Ricci AJ, Cheng AG. Mechanisms of aminogly­ coside ototoxicity and targets of hair cell protection. Int J Otolaryngol. 2011; 937861 . doi: 10.1155/2011.937861. Epub 2011 Oct 25. 91. Seaman BJ, Guardiani EA, Brewer CC, et al. Audiovestibular dysfunction associated with adoptive cell immunotherapy for melanoma. Otolaryngol Head Neck Surg. 2012;147:744-9.

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CHAPTER

20

Tinnitus Carol Bauer

Incidence and Prevalence The prevalence of tinnitus in the adult population is estimated to range from 6% to 19% of adults, depending on the population sampled and the definition of tinnitus used in the survey.1 The most conservative estimate of tinnitus would indicate that 24 million people in the United States experience tinnitus.2 Risk factors for tinnitus have been identified from large epidemiological surveys and include nonmodifiable factors of gender (male) and ethnicity (non-Hispanic Whites), and modifiable factors including body mass index (≥ 30 kg/m2), hypertension, diabetes mellitus, dyslipidemia, anxiety disorder, noise exposure, and smoking.3 Estimates of the range of tinnitus severity vary with the definition used, the survey instrument and the demo graphic population sampled. Population studies that assess the severity and impact of tinnitus are significantly  

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Subjective tinnitus is an auditory perception without an external acoustic source. The sensation is not a modern malady, and references to tinnitus are found in some of the earliest medical manuscripts. Tinnitus is a symptom associated with a wide range of etiologies and pathologic mechanisms, from conductive hearing loss secondary to cerumen impaction and otosclerosis, from turbulent blood flow in an intracranial vessel or enhanced blood flow in a glomus jugulare tumor, from acute acoustic trauma with temporary threshold shift to age-related sensorineural hearing loss, from auditory hallucinations to hearing loss secondary to vestibular schwannomas. Tinnitus that occurs in association with sensorineural hearing loss (age-related, noise-induced, related to ototoxins, or otherwise idiopathic) is termed primary tinnitus. Tinnitus that can be linked to a specific cause or organic condition is termed secondary tinnitus. The wide range of causative pathology dictates a thorough evaluation of the tinnitus complaint. The experience of tinnitus and the impact of tinnitus on daily life is highly individual, and can range from minimal to severe. Fortunately, severely disturbing tinnitus affects  95% of tinnitus in MD patients can be successfully managed with simple directive counseling.61 Many other modalities have been proposed, none can be recommended because of lack of compelling medical evidence.

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Chapter 21: Meniere’s Disease





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In the absence of relevant clinical studies, the management of MD remains empirical, with the use of lifestyle changes, pharmacotherapy, office based procedures, and surgery. The development of transtympanic therapies represents a true advance in therapeutics that has largely supplanted surgical intervention. Only with increasing understanding through continued high quality basic, translational, and clinical research can we shift our management paradigm from that of control to that of cure.

therapy in Meniere’s disease: have they been applied in the published literature of the last decade? Clin Otolaryngol Allied Sci. 2003;28(3):173 6. Rauch SD, Zhou G, Kujawa SG, et al. Vestibular evoked myogenic potentials show altered tuning in patients with Meniere’s disease. Otol Neurotol. 2004; 25(3):333 8. Helling K, Schonfeld U, Clarke AH. Treatment of Meniere’s disease by low dosage intratympanic gentamicin applica­ tion: effect on otolith function. Laryngoscope. 2007;117(12): 2244 50. Young YH. Potential application of ocular and cervical ves­ tibular evoked myogenic potentials in Meniere’s disease: a review. Laryngoscope. 2013;123(2):484 91. Coelho DH, Roland JT, Jr., Golfinos JG. Posterior fossa meningiomas presenting with Meniere’s like symptoms: case report. Neurosurgery. 2008;63(5):E1001; discussion E. Niyazov DM, Andrews JC, Strelioff D, et al. Diagnosis of endolymphatic hydrops in vivo with magnetic resonance imaging. Otol Neurotol. 2001;22(6):813 7. Nakashima T, Naganawa S, Sugiura M, et al. Visualization of endolymphatic hydrops in patients with Meniere’s dis­ ease. Laryngoscope. 2007;117(3):415 20. Nakashima T, Naganawa S, Teranishi M, et al. Endolymphatic hydrops revealed by intravenous gadolinium injection in patients with Meniere’s disease. Acta Otolaryngol. 2010;130(3):338 43. Fukuoka H, Takumi Y, Tsukada K, et al. Comparison of the diagnostic value of 3 T MRI after intratympanic injec­ tion of GBCA, electrocochleography, and the glycerol test in patients with Meniere’s disease. Acta Otolaryngol. 2012;132(2):141 5. Coelho DH, Lalwani AK. Medical management of Meniere’s disease. Laryngoscope. 2008;118(6):1099 108. Babin RW, Balkany TJ, Fee WE. Transdermal scopolamine in the treatment of acute vertigo. Ann Otol Rhinol Laryngol. 1984;93(1 Pt 1):25 7. Pyykko I, Magnusson M, Schalen L, et al. Pharmacological treatment of vertigo. Acta Otolaryngol Suppl. 1988; 455: 77 81. Fisher LM, Derebery MJ, Friedman RA. Oral steroid treat­ ment for hearing improvement in Meniere’s disease and endolymphatic hydrops. Otol Neurotol. 2012;33(9):1685 91. Morse GG, House JW. Changes in Meniere’s disease responses as a function of the menstrual cycle. Nurs Res. 2001;50(5):286 92. Soderman AC, Moller J, Bagger Sjoback D, et al. Stress as a trigger of attacks in Meniere’s disease. A case crossover study. Laryngoscope. 2004;114(10):1843 8. Kinney SE, Sandridge SA, Newman CW. Long term effects of Meniere’s disease on hearing and quality of life. Am J Otol. 1997;18(1):67 73. Coker NJ, Coker RR, Jenkins HA, et al. Psychological pro­ file of patients with Meniere’s disease. Arch Otolaryngology Head Neck Surg. 1989;115(11):1355 7. Furstenberg AC, Lashmet FH, Lathrop F. Meniere’s symp­ tom complex: medical treatment. 1934. Ann Otol Rhinol Laryngol. 1992;101(1):20 31. -

CONCLUSION

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18a.

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1. Antonio SM, Friedman R. Meniere’s disease. In: Jackler RK, Brackmann DE (eds), Neurotology. Philadelphia, PA: Elsevier; 2005. pp. 621 38. 2. Hallpike CS, Cairns H. Observations on the pathology of Meniere’s syndrome: (section of otology). Proc R Soc Med. 1938;31(11):1317 36. 3. Kimura RS. Experimental blockage of the endolymphatic duct and sac and its effect on the inner ear of the guinea pig. A study on endolymphatic hydrops. Ann Otol Rhinol Laryngol. 1967;76(3):664 87. 4. Schuknecht HF. The pathophysiology of Meniere’s disease. Am J Otol. 1984;5(6):526 7. *5. Salt AN, Plontke SK. Endolymphatic hydrops: pathophysi­ ology and experimental models. Otolaryngol Clin N Am. 2010;43(5):971 83. *6. Merchant SN, Adams JC, Nadol JB, Jr. Pathophysiology of Meniere’s syndrome: are symptoms caused by endolym­ phatic hydrops? Otol Neurotol. 2005;26(1):74 81. 7. Semaan MT, Alagramam KN, Megerian CA. The basic sci­ ence of Meniere’s disease and endolymphatic hydrops. Curr Opin Otolaryngol Head Neck Surg. 2005;13(5):301 7. 8. Hietikko E, Kotimaki J, Okuloff A, et al. A replication study on proposed candidate genes in Meniere’s disease, and a review of the current status of genetic studies. Int J Audiol. 2012;51(11):841 5. *9. Derebery MJ. Allergic and immunologic features of Meniere’s disease. Otolaryngol Clin N Am. 2011;44(3):655 66, ix. 10. Minor LB, Schessel DA, Carey JP. Meniere’s disease. Curr Opin Neurol. 2004;17(1):9 16. 11. Kitahara M. Bilateral aspects of Meniere’s disease. Meniere’s disease with bilateral fluctuant hearing loss. Acta Otolary­ ngol Suppl. 1991;485:74 7. 12. Paparella MM. Pathogenesis and pathophysiology of Meniere’s disease. Acta Otolaryngol Suppl. 1991;485:26 35. 13. Morrison AW, Johnson KJ. Genetics (molecular biology) and Meniere’s disease. Otolaryngol Clin N Am. 2002;35(3): 497 516. 14. Thorp MA, Shehab ZP, Bance ML, et al. Hearing A HCo, Equilibrium. The AAO HNS Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of





18.

REFERENCES

*References with asterisks refer to critical sources.

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31. Thai-Van H, Bounaix MJ, Fraysse B. Meniere’s disease: patho­ physiology and treatment. Drugs. 2001;61(8):1089-102. 32. Claes J, Van de Heyning PH. Medical treatment of Meniere’s disease: a review of literature. Acta Otolaryngol Suppl. 1997;526:37-42. 33. Di Berardino F, Filipponi E, Alpini D, et al. Meniere disease and gluten sensitivity: recovery after a gluten-free diet. Am J Otolaryngol. 2013;34(4):355-6. 34. Thirlwall AS, Kundu S. Diuretics for Meniere’s disease or syndrome. Cochrane Database Syst Rev. 2006 (3):CD003599. 35. Klockhoff I, Lindblom U. Meniere’s disease and hydro­ chlorothiazide (Dichlotride)—a critical analysis of symp­ toms and therapeutic effects. Acta Otolaryngol. 1967;63(4): 347-65. 36. Ruckenstein MJ, Rutka JA, Hawke M. The treatment of Meniere’s disease: Torok revisited. Laryngoscope. 1991;101 (2):211-8. 37. van Deelen GW, Huizing EH. Use of a diuretic (Dyazide) in the treatment of Meniere’s disease. A double-blind crossover placebo-controlled study. ORL J Otorhinolaryngol Rel Spec. 1986;48(5):287-92. 38. Timmerman H. Pharmacotherapy of vertigo: any news to be expected? Acta Otolaryngol Suppl. 1994;513:28-32. 39. Fraysse B, Bebear JP, Dubreuil C, Berges C, Dauman R. Beta­ histine dihydrochloride versus flunarizine. A double-blind study on recurrent vertigo with or without cochlear syn­ drome typical of Meniere’s disease. Acta Otolaryngologica Suppl. 1991;490:1-10. 40. James AL, Burton MJ. Betahistine for Meniere’s disease or syndrome. Cochrane Database Syst Rev. 2001;(1):CD001873. 41. Black FO, Pesznecker SC. Vestibular ototoxicity. Clinical considerations. Otolaryngol Clin N Am. 1993;26(5):713-36. 42. Hirsch BE, Kamerer DB. Role of chemical labyrinthectomy in the treatment of Meniere’s disease. Otolaryngol Clin N Am. 1997;30(6):1039-49. 43. Ishiyama G, Lopez I, Baloh RW, et al. Histopathology of the vestibular end organs after intratympanic gentamicin fail­ ure for Meniere’s disease. Acta Otolaryngol. 2007;127(1): 34-40. *44. Cohen-Kerem R, Kisilevsky V, Einarson TR, et al. Intra­ tympanic gentamicin for Meniere’s disease: a meta-analy­ sis. Laryngoscope. 2004;114(12):2085-91. 45. Harner SG, Driscoll CL, Facer GW, et al. Long-term followup of transtympanic gentamicin for Meniere’s syndrome. Otol Neurotol. 2001;22(2):210-14. 46. Rarey KE, Gerhardt KJ, Curtis LM, et al. Effect of stress on cochlear glucocorticoid protein: acoustic stress. Hear Res. 1995;82(2):135-8.

47. Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmaco­ kinetics in the inner ear fluids: an animal study followed by clinical application. Laryngoscope. 1999;109(7 Pt 2):1-17. 48. Chandrasekhar SS, Rubinstein RY, Kwartler JA, et al. Dexa­ methasone pharmacokinetics in the inner ear: comparison of route of administration and use of facilitating agents. Otolaryngol Head Neck Surg. 2000;122(4):521-8. *49. Silverstein H, Isaacson JE, Olds MJ, et al. Dexamethasone inner ear perfusion for the treatment of Meniere’s disease: a prospective, randomized, double-blind, crossover trial. Am J Otol. 1998;19(2):196-201. 50. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alterna­ tive medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998;280(18):1569-75. 51. Densert B, Densert O, Erlandsson B, et al. Trans­mission of square wave pressure pulses through the peril­ym­phatic fluid in cats. Acta Otolaryngol. 1986;102(3-4):186-93. 52. Gates GA, Verrall A, Green JD, Jr, et al. Meniett clinical trial: long-term follow-up. Arch Otolaryngol Head Neck Surg. 2006;132(12):1311-6. 53. Gottshall KR, Hoffer ME, Moore RJ, Balough BJ. The role of vestibular rehabilitation in the treatment of Meniere’s disease. Otolaryngol Head Neck Surg. 2005;133(3):326-8. 54. Soderman AC, Bergenius J, Bagger-Sjoback D, et al. Patients’ subjective evaluations of quality of life related to diseasespecific symptoms, sense of coherence, and treatment in Meniere’s disease. Otol Neurotol. 2001;22(4):526-33. 55. Chung JW, Fayad J, Linthicum F, Ishiyama A, Merchant SN. Histopathology after endolymphatic sac surgery for Meniere’s syndrome. Otol Neurotol. 2011;32(4):660-4. *56. Pullens B, Verschuur HP, van Benthem PP. Surgery for Meniere’s disease. Cochrane Database Syst Rev. 2013;2: CD005395. 57. Gibson WP. Hypothetical mechanism for vertigo in Meniere’s disease. Otolaryngol Clin N Am. 2010 Oct;43(5):1019-27. 58. Charpiot A, Rohmer D, Gentine A. Lateral semicircular canal plugging in severe Meniere’s disease: a clinical prospec­ tive study about 28 patients. Otol Neurotol. 2010;31(2): 237-40. 59. Loader B, Beicht D, Hamzavi JS, et al. Tenotomy of the middle ear muscles causes a dramatic reduction in ver­ tigo attacks and improves audiological function in definite Meniere’s disease. Acta Otolaryngol. 2012;132(5):491-7. 60. Gacek RR, Gacek MR. Comparison of labyrinthectomy and vestibular neurectomy in the control of vertigo. Laryngo­ scope. 1996;106(2 Pt 1):225-30. 61. Feenstra L. The management of tinnitus with or without Meniere’s disease. Acta Otolaryngol Suppl. 1997;526:47-9.

*References with asterisks refer to critical sources.

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CHAPTER

22

Temporal Bone Trauma J Caleb Simmons, Alex D Sweeney, Marc-Elie Nader, Robert A Williamson

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PATHOGENESIS

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Temporal bone fractures are relatively common in the setting of closed head trauma across all age groups. Can­ non and Jahrsdoerfer demonstrated in a series of 1300 consecutive head trauma patients that approximately 22% of skull fractures included a fracture of the temporal bone.5 Additionally, upwards of 40% of patients with basilar skull fractures have been reported to have a temporal bone fracture.6 These rates may differ based on age. Previous reports have identified temporal bone fractures following head trauma in 30 75% of adults7,8 versus 6 14% of pedia­ tric patients.9 These differences may be explained by the relative elasticity of the less pneumatized and less fused pediatric temporal bone versus that of the adult, though evidence does suggest that even the adult skull retains the ability to deform before fracturing occurs.10 Both -





The complex structure of the temporal bone reflects its functional importance. Occupying the majority of the late­ ral skull base, the temporal bone is composed of multiple bony subunits, the contents of which are crucial to our interactions with the surrounding world. It houses major arterial and venous structures, serves as a rigid bound­ ary of the middle and posterior cranial fossae, acts as an important gateway between the intracranial contents and the head and neck, and acts as a receiver for information essential to proper hearing and balance. Undoubtedly, temporal bone injury can be catastrophic in many ways. The development of the temporal bone is important to consider in the setting of traumatic injury. In utero, the temporal bone develops as a hybrid of intramembra­ nous (squamous and tympanic) and intracartilaginous (petrous and mastoid) bone formation.1 Ossification in these different locations progresses at varying rates, and the end result is bony fusion along planes that are pre­ served as suture lines in the adult temporal bone. As the temporal bone grows, it begins to aerate from within. Pneumatization begins as a consequence of prenatal expansion within the tympanic cavity, and it can con­ tinue for years following birth.2,3 The developed temporal bone thus may have intrinsic weaknesses along suture lines and its more aerated portions.4 Anatomically, the temporal bone can be divided into four subunits: petrous, squamous, tympanic, and mastoid. These divisions are most relevant in terms of the struc­ tures contained within each portion. The petrous portion of the temporal bone is located medially and anteriorly

and contains the carotid artery, cochlea, labyrinth and the labyrinthine segment of the facial nerve, which includes the geniculate ganglion. It also comprises the bony portion of the internal auditory canal. The tympanic segment of the temporal bone contains the tympanic membrane (TM), ossicles, and the horizontal segment of the facial nerve. The mastoid segment contains the vertical segment of the facial nerve, the transverse/sigmoid sinus and jugular bulb. Additionally, the inferior most aspect of the mastoid portion—the mastoid tip—is an insertion point for neck musculature such as the posterior belly of the digastric, the sternocleidomastoid, and splenius capitus. The squamous portion of the temporal bone serves as a shield over the temporal lobe of the brain.

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INTRODUCTION

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populations appear to have a bimodal age distribution. Pediatric temporal bone trauma occurs more often around the ages 3 and 12,11 while adult trauma in the adult population occurs more commonly in the 20s and 50s.4 There is a male preponderance in both adults and chil­ dren, though there appears to be less of a signi­ficant gender difference in the pediatric population (62.5% males in children versus 81.7% in adults).4 In both age groups, fractures are unilateral in > 90% of cases.4 The common mechanisms of temporal bone trauma depend somewhat on the patient population. In Cannon and Jarsdoerfer’s series of 1300 consecutive head trauma patients, 44% occurred as a result of automobile collisi­ons. Automobile and bicycle accidents account for a signifi­ cant portion of pediatric injuries, as well.5 Children under the age of 4 may be just as likely to have trauma due to falls.4,11 Penetrating trauma in the form of gunshot wounds represents a smaller percentage of temporal bone injuries, though some reports suggest that there are trends toward increased penetrating temporal bone trauma due to gun violence in urban areas of the United States.12 Two of the most important considerations in the eval­ uation of temporal bone trauma are the mechanism of the trauma and the distribution of the trauma within the temporal bone. Whether penetrating or blunt, all trauma is the result of force and energy transfer from one struc­ ture to another. The degree of trauma, therefore, should be directly proportional to the mass of the object striking the temporal bone, directly proportional to the change in acceleration of that object as it strikes the temporal bone and exponentially proportional to the velocity of that object. As such, knowledge of the specific trauma mecha­ n­ism can be critical in predicting the extent of injury, especially when considering the differences between trau­matic forces such as a rifle round and an automobile windshield. Specifically in cases of penetrating gunshot wounds, considerations of muzzle velocity and ammu­ nition caliber could prove helpful. The location of temporal bone trauma may correlate with post-traumatic functional deficits. When blunt force is applied to the temporal bone, it is thought to dissipate along vectors that are predictable based on the orienta­ tion of the trauma. Blunt occipital trauma, where force is deli­vered perpendicular to the long access of the tem­ poral bone, is generally associated with transverse frac­ tures. Furthermore, longitudinal fractures are more frequently seen when the lateral aspect of the temporal bone absorbs a forceful blow.13 Traditionally, temporal bone fractures have been characterized in terms of their

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orientation to the long axis of the petrous pyramid as longitudinal or transverse, the former being identified in approximately 80% of cases. However, newer studies have suggested that as many as 75% of fractures are actually oblique,14 and characterization of fractures as oblique, lon­gitudinal, and transverse nomenclature does not corre­ late well with clinical findings other than sensorineural hearing loss (SNHL).4,15 This has led to the introduction of different classification systems that may have better clinical correlation, including otic-capsule-sparing versus otic-capsule-violating,6,16,17-18 petrous versus nonpetrous,15 and another system based on the four parts of the tempo­ ral bone (squama, tympanic, mastoid, and petrous)4. For example, describing fractures based on their involvement of the otic capsule or the petrous bone may be more pre­ dictive of facial nerve injury, cerebrospinal fluid (CSF) leak, and type of hearing loss (Table 22.1). No system has gained widespread acceptance as yet, though clinical correlation and utility seem to be highest with the otic capsule sparing/nonsparing classification. Otic violation resulted in complete ipsilateral SNHL in Figures 22.1 and 22.2, as well as facial nerve weakness that resolved in the case of Figures 22.1A to D and did not in the case of Figures 22.2A to C. A CSF leak was a sequela of the oticviolating fracture in Figures 22.3A and B; the leak resolved with conservative manage­ ment. Otic-sparing fractures are demonstrated in Figures 22.4 and 22.5, resulting in conductive hearing loss (CHL) that resolved in Figures 22.4A and B and did not in Figures 22.5A and B.

CLINICAL FINDINGS: SYMPTOMS AND SIGNS As discussed above, the findings associated with tempo­ ral bone trauma can vary widely depending on the mechanism and location of trauma. In general, an initial evaluation should begin with an in-depth history that can elicit the specific circumstances surrounding an injury (including ballistics information, when applicable) and functional deficits immediately following injury. The initial physical examination should identify associated soft tissue injury, realizing that some findings, such as an auricular hematoma, require immediate attention. Additionally, given the frequency with which temporal bone injuries can involve the carotid canal (52%) and jugular bulb (21%)19, massive bleeding should be quickly recognized and stabilized. Ecchymosis along the skull base is com­ monly seen in basilar skull fractures. Battle’s sign (occipital ecchymosis) and the so-called “raccoon eyes” (periorbi­tal

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Table 22.1: Three systems of classification of pattern of temporal bone fractures and their functional relevance

Incidence 50% 27% 23% 80% 20%

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-

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Longitudinal* Transverse Oblique p value Otic capsule sparing* Otic capsule violating p value Petrous** Nonpetrous p value

11.6 99.4

SNHL 20 25 28.6 Not (p=0.34) 4 100 p0.99) 12 67 p2 cm, then MRI should be performed to rule out potential herniation of intracra­ nial contents into the mastoid or middle ear, which may change surgical approach.48 Complications may occur in the presence of a CSF leak. The rate of meningitis in patients with temporal bone fractures and CSF leak has been demonstrated to be 7–10%16,49; the most significant risk factors were a leak persisting >7 days and the presence of a concurrent infection elsewhere. However, prophylactic antibiotics effective against the most common pathogen causing meningitis, Pneumococcus spp., have led to a significant reduction in its incidence.50 Routine use in trauma cases is controversial, however. Pneumocephalus may occur when air is introduced into the cranial cavity and sealed within by a ball valve defect in the dura. The development of air within the dura is a potentially lethal complication, possibly resulting in intracranial hypertension and possible brain herniation.51 If neurologic examination changes or if pneumocephalus is persistent, then aggressive manage­ ment with the assistance of a neurosurgeon is indicated. Initially, CSF leak can be managed with conservative measures as the majority of leaks will close spontaneously. Patients are instructed to maintain bed rest, elevate the head of the bed, and avoid straining with the use of stool softeners.16 Spontaneous resolution with conservative management occurred in 95–100% of patients, with closure occurring in the first 7 days in 78% and between 8 and 14 days in 95%.16,47 Placement of a lumbar drain can

also be useful for persistent cases lasting 5–7 days after injury. The catheter is inserted into the subarachnoid space by aseptic lumbar puncture and left in place under sterile dressing. CSF is released through the catheter in a controlled fashion and at a defined rate to lessen the pressure differential across the dural defect and allow more expedient spontaneous closure. CSF leaks that persist beyond the first 7 days despite these conservative methods, patients with recurrent meningitis, or patients with persistent pneumocephalus, will likely require surgical repair.52 The proportion of patients with persistent CSF leak who require surgical repair appears to be approximately 5%.16,47 Based on CT imaging and localization and extent of the defect, the approaches may include middle ear, mastoid, or middle fossa exposure. Depending on the size and shape of the defect, soft tissue or cartilage may be obtained for multi­ layer closure, usually reinforced by bone pate or free fragments or grafts taken from the mastoid in order to stabilize the repair against continuous CSF pulsation pres­ sure and gravity. Depending on extent and persistence of the leak, temporal bone obliteration with abdominal fat grafting may be considered, possibly including removal of the TM and squamous elements of the EAC, with closure of the EAC. This latter option will result in a maximal CHL, and thus is particularly useful when sensorineural func­ tion has already been lost.

CSF Leak

355

Conductive Hearing Loss Conductive hearing loss is demonstrated more often in temporal bone fracture lines involving the attic and posterosuperior EAC wall. Associations of CHL with classi­ fications of fracture lines may be seen in Table 22.1. Dislocation of the ossicles is frequently suggested on

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audiometry with a persistent air-bone gap of >20 dB, and may be seen on CT imaging as in Figures 22.5A and B. On middle ear exploration, incudostapedial dislocation is the most common finding (11–14%), followed by dislocation of the incudomallear joint, fracture of the stapes supra­ structure (7%), and last malleus fracture (1%).5,19 Children appear to have an increased incidence of stapes fracture, possibly secondary to increased deformity of the pediatric skull.53 Initial management is typically conservative, allowing for recovery from injury and clearance of blood products from the middle ear, TM injury and blood products in the EAC. However, if surgery is indicated for other reasons (e.g. facial nerve decompression or CSF leak repair), it may be appropriate to perform ossiculoplasty at that time.39 Fractures of the distal long process of the malleus near the umbo may be treated by excision of the fractured segment and tympanoplasty with temporalis fascia. More proximal malleus fractures may require removal of the malleus and either incus transposition or placement of prosthesis. Dislocation of the incus may be treated with either incus transposition, placement of prosthesis, or more conservatively with careful reduction of the dislocation and packing of the mastoid and middle ear. Rarely, in patients with large skull base defects or after middle cranial fossa surgery, CHL can occur due to dura contacting the heads of the ossicles, resulting in a dampening of transmission. The hearing loss is generally minimal but may require skull base repair to correct, particularly with large defects or herniation.48 Prognosis for CHL is generally good, with closure of air-bone gap in most studies to within 10dB.45

Sensorineural Hearing Loss Sensorineural hearing loss can occur after temporal bone trauma due to five proposed mechanisms: (1) direct injury to the acoustic nerve; (2) direct injury to the otic capsule with disruption of the membranous labyrinth, vascular vasospasm, thrombosis, or hemorrhage into the inner ear; (3) perilymphatic fistula; (4) occlusion of the vestibular aqueduct by the fracture line, followed by endolymphatic hydrops; and (5) pressure waves transmitted directly the cochlea, resulting in damage to the organ of Corti and concussion of the temporal bone without appreciable fracture lines.54 Examples of otic-violating fractures result­ ing in complete SNHL may be seen in Figures 22.1 to 22.3. Any sensorineural component evident on audiometry at 4–6 weeks is typically permanent and is not expected

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to improve with surgery. Patients with mild to moderate SNHL are treated with standard amplification. In patients with unilateral profound SNHL, bone-anchored hearing aids have traditionally been the best option for rehabi­ litation and to decrease the head-shadow effect. Temporal bone fracture may result in bilateral severe to profound SNHL however, and these patients may be candidates for cochlear implantation. Patients must be properly selected: there must be no significant bony discontinuity or coch­ lear ossification.55-56 If a transverse temporal bone fracture occurs through the internal auditory canal, the postgan­ glionic cochlear nerve may be injured, rendering cochlear implantation useless. If this type of injury is bilateral, an auditory brain stem implant (ABI) may be the only option for auditory rehabilitation, but these injuries are typically severe and often not survivable. Some surgeons recommend promontory testing to demonstrate an intact cochlear nerve (VIII) before implantation, though this test does not have high enough negative predictive value to preclude confidence interval (CI). High-resolution CT or heavily T2-weighted MRI sequences may be useful for establishing cochlear anatomy and patency, but shortly, the only method by which one may be sure a patient will not tolerate or benefit from CI is a CI trial.63 Cochlear implantation in the ipsilateral ear in patients deafened by temporal bone fracture has resulted in 70-100% openset sentence recognition. These results were found to be superior to ABI results in similar patients.54 One study demonstrated a complication of facial nerve stimulation by CI through fracture lines in 2 of 7 patients with deaf­ ness due to temporal bone implantation. These two CIs required explantation, but the patients were able to be implanted in the contralateral ear with good hearing rehabilitation and no facial nerve stimulation.55 Auditory brain stem implantation has been proposed as a secondline treatment for patients who fail CI.

Vestibular Injury/Dysfunction Vertigo may be a complication of temporal bone fracture and must be fully investigated to determine etiology and help guide treatment. Short-term vestibular suppressants may be used to manage acute symptoms but chronic use prevents vestibular adaptation and rehabilitation, and should be avoided. Vestibular function testing may be helpful in analyzing the vestibular system and discerning the etiology of new-onset, postinjury vertigo. Benign paroxysmal positional vertigo (BPPV) is cer­ tainly the most common etiology of vertigo after head

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initial temporal bone trauma.60 Presentation is generally with onset of CSF otorrhea, unilateral clear middle ear effusion, or recurrent meningitis. HRCT and MRI imaging may be required for proper diagnosis and surgical plan­ ning, and a combined mastoid and middle cranial fossa may be required for repair, similar to the previous dis­ cussion on CSF leaks. Cholesteatoma attributable to a history of temporal bone trauma is rare with fewer than 20 reported cases.61 Presentation may be 2–24 years after the initial injury. The development of this sequela may be due to a penetra­ ting injury or fracture line seeding epithelial elements from the skin or EAC canal into the temporal bone. In one case series, 15% of patients surviving gunshot wounds to the temporal bone later developed secondary cholestea­ toma requiring mastoidectomy.16 Cholesteatomas from this mechanism are frequently extensive since the mastoid is typically well pneumatized and allows for uninhibited spread of the squamous elements. There have been case reports of otogenic brain abscesses due to infected choles­ teatomas within fracture lines.61 Mastoidectomy, including possible canal wall down or radical techniques, has been advocated as the primary treatment for penetrating gun­ shot wounds, as residual bullet fragments may remain lodged in the bone and become a nidus for infection as well.24 Patients with temporal bone fracture, particularly those violating the otic capsule, should be informed that they have an increased long term risk for meningitis, estimated to be as high as 15%.54 This is hypothesized to be secondary to the fibrous nature of the endochondral bone of the otic capsule, which is more porous than the native bone.50,62 One case report illustrated the seriousness of this com­ plication with a patient with remote history of temporal bone fracture who progressed from acute otitis media to lethal meningitis. Histopathologic analysis of the tempo­ ral bone after death showed acute purulent labyrinthitis within an old fracture line filled with fibrous tissue. The fracture line extended into the internal auditory canal and thus provided acquired access to the meningeal space.62 In the event of such a complication, the meningitis should be treated per normal protocol. When resolved, the patient should be treated with labyrinthectomy and fat graft obliteration with closure of the EAC. -

-

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trauma, usually developing days to weeks after the initial injury. BPPV symptoms are caused by traumatic displace­ ment of otoconia into the ampulla of the semicircular canals, typically the posterior canal. Treatment is by stan­ dard repositioning maneuvers and rehabilitation. The prognosis is excellent with this therapy. Perilymph fistula may occur at the oval or round win­ dow and may involve subluxation of the stapes footplate. This is typically treated with either repair or obliteration of niches during middle ear exploration.5 Preservation of residual auditory and vestibular function, as well as resolution of symptoms, has been reported with surgical repair.5,57 When perilymph fistula has been ruled out, post traumatic endolymphatic hydrops may be considered as an etiology for a trauma patient’s vertigo. This is likely to occur in a delayed fashion after temporal bone injury, possibly secondary to occlusion of the vestibular aque­ duct by the fracture line or healing process.57 This com­ plication is typically ongoing and chronic, with a similar prognosis to Meniere’s disease. These patients usually first undergo medical management similar to Meniere’s disease with low salt diet, steroids, and diuretics. Usually the indications for intervention or surgical management follow the indications for management of Meniere’s disease after failed trials of medical therapy.

357

REFERENCES 1. Bailey FR, Miller AM. Text Book of Embryology. New York, NY: William Wood and Co. -

Various other rare sequelae of temporal bone trauma have been reported, and can be quite delayed. Meningocele or encephalocele may present from 1 to 21 years after the



OTHER SEQUELAE



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Rarely, temporal bone fractures may present with palsies of other cranial nerves, usually V through XI. Penetra­ ting injuries to the temporal bone may be extensive and comminuted, involving multiple foramina. Longitudinal fractures may extend to foramen ovale, while transverse may extend to foramen spinosum or lacerum.24 The ratio­ nale for the timing of surgical intervention follows that of the facial nerve. If there was immediate onset of paraly­ sis after injury, some authors advocate exploration. In the cases of delayed onset, expectant monitoring is usually advised and spontaneous recovery is the usual out­ come.58 59 Ongoing lower cranial nerve functional deficits, though unusual, can typically be rehabilitated according to current clinical guidelines for nontraumatic causes.

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Associated Lower Cranial Nerve Injury

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2. Nemzek WR, Brodie HA, Chong BW, et al. Imaging findings of the developing temporal bone in fetal specimens. Am J Neuroradiol. 1996;17(8):1467-77. 3. Virapongse C, Sarwar M, Bhimani S, et al. Computed tomo­rgraphy of temporal bone pneumatization: 1. Normal pattern and morphology. AJR. 1985;145:473-81. 4. Kang HM, Kim MG, Boo SH, et al. Comparison of the clini­ cal relevance of traditional and new classification systems of temporal bone fractures. Eur Arch Otorhinolaryngol. 2012;269:1893-9. 5. Cannon CR, Jahrsdoerfer RA. Temporal bone fractures. Review of 90 cases. Arch Otolaryngol. 1983;109(5):285-8. 6. Dahiya R, Keller JD, Litofsky NS, et al. Temporal bone frac­ tures: otic capsule sparing versus otic capsule violating clinical and radiographic considerations. J Trauma. 1999; 47(6):1079-83. 7. Hass AN, Ledington JA. Traumatic injuries of the temporal bone. Otolaryngol Clin North Am. 1988;21:295-316. 8. Wiet RJ, Valvassori GE, Kotsanis CA, et al. Temporal bone fractures: state of the art review. Am J Otolaryngol. 1985; 6:207-15. 9. McGuirt WF Jr., Stool SE. Temporal bone fractures in children: A review with emphasis on long-term sequelae. Clin Pediatr. 1992;31:12-8. 10. Yoganandan N, Pintar FA. Biomechanics of temporo-pari­ etal skull fracture. Clinical Biomechanics. 2004;19:225-39. 11. Lee D, Honrado C, Har-El G, et al. Pediatric temporal bone fractures. Laryngoscope. 1998;108(6):816-21. 12. Alvi A, Bereliani A. Acute intracranial complications of tem­ poral bone trauma. Otolaryngol Head Neck Surg. 1998;119 (6):609-13. 13. Spector GJ. Developmental temporal bone anatomy and its clinical significance: variations on themes by H.F. Schuknecht. Ann Otol Rhinol Laryngol Suppl. 1984;112:101-9. 14. Ghorayeb BY, Yeakley JW. Temporal bone fractures: lon­ gitudinal or oblique? The case for oblique temporal bone fractures. Laryngoscope. 1992;102:129-34. 15. Ishman SL, Friedland DR. Temporal bone fractures: tradi­ tional classification and clinical relevance. Laryngoscope. 2004;114(10):1734-41. 16. Brodie HA, Thompson TC. Management of complications from 820 temporal bone fractures. Am J Otol. 1997; 18(2):188-97. 17. Kelly KE, Tami TA. Temporal bone and skull base trauma. In: Jackler RK, Brackmann DE (eds), Neurotology. St Louis: Mosby; 1994. pp. 1127-47. 18. Little SC, Kesser BW. Radiographic classification of temporal bone fractures: clinical predictability using a new system. Arch Otolaryngol Head Neck Surg. 2006;132(12):1300-4. 19. Wysocki J. Cadaveric dissections based on observations of injuries to the temporal bone structures following head trauma. Skull Base. 2005;15(2):99-106. 20. Lew HL, Lee EH, Miyoshi Y. Brainstem auditory-evoked potentials as an objective tool for evaluating hearing dys­ function in traumatic brain injury. Am J Phys Med Rehabil. 2004;83(3):210-15.

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21. Katsarkas A. Benign paroxysmal positional vertigo (BPPV): idiopathic versus post-traumatic. Acta Otolaryngol. 1999; 119(7):745-9. 22. Fisch U. Management of intratemporal facial nerve inju­ ries. J Laryngol Otol. 1980;94(1):129-34. 23. Dula DJ, Fales W. The ‘ring sign’: is it a reliable indicator for cerebral spinal fluid? Ann Emerg Med. 1993;22(4):718-20. 24. Jenkins HA, Ator GA, Chen HH. Traumatic facial paraly­ sis. In: Brackmann DE, Shelton C, Arriaga MA, et al. (eds), Otologic Surgery, 3rd edition. Philadelphia, PA: Saunders; 2010. pp. 347-361. 25. Johnson DW, Hasso AN, Stewart CE, et al. Temporal bone trauma: high-resolution computed tomographic evalua­ tion. Radiology. 1984;151(2):411-5. 26. Holland BA, Brant-Zawadzki M. High-resolution CT of tem­ poral bone trauma. AJR Am J Roentgenol. 1984;143(2):391-5. 27. Brodie HA. Management of temporal bone trauma. In: Flint PW, Haughey BH, Lund VJ, et al. (eds), Cummings Otolaryngology Head & Neck Surgery. Philadelphia: Elsevier; 2010. 28. Zimmerman RA, Bilaniuk LT, Hackney DB, Goldberg HI, Grossman RI. Magnetic resonance imaging in temporal bone fracture. Neuroradiology. 1987;29(3):246-51. 29. Haberkamp TJ, Harvey SA, Daniels DL. The use of gadolin­ ium-enhanced magnetic resonance imaging to determine lesion site in traumatic facial paralysis. Laryngoscope. 1990;100(12):1294-300. 30. Kerwin AJ, Bynoe RP, Murray J, et al. Liberalized screening for blunt carotid and vertebral artery injuries is justified. J Trauma. 2001;51(2):308-14. 31. Chang CY, Cass SP. Management of facial nerve injury due to temporal bone trauma. Am J Otol. 1999;20:96-114.  32. Nash JJ, Friedland DR, Boorsma KJ, et al. Management and outcomes of facial paralysis from intratemporal blunt trauma: a systematic review. Laryngoscope. 2010;120 Suppl 4:S214. 33. Darrouzet V, Duclos JY, Liguoro D. Management of facial paralysis resulting from temporal bone fractures: Our expe­ rience in 115 cases. Otolaryngol Head Neck Surg. 2001; 125:77-84. 34. McKennan KX, Chole RA. Facial paralysis in temporal bone trauma. Am J Otol. 1992;13:167-72. 35. Coker NJ, Fordice JO, Moore S. Correlation of the nerve excitability test and electroneurography in acute facial paralysis. Am J Otol. 1992;13:127-33. 36. Fisch U. Facial paralysis in fractures of the petrous bone. Laryngoscope. 1974;84:2141-54. 37. Shindo ML, Fetterman BL, Shih L. Gunshot wounds of the temporal bone: A rational approach to evaluation and man­ agement. Otolaryngol Head Neck Surg. 1995;112:533-9. 38. Duncan NO 3rd, Coker NJ, Jenkins HA, et al. Gunshot inju­ ries of the temporal bone. Otolaryngol Head Neck Surg. 1986;94:47-55. 39. Hato N, Nota J, Hakuba N, et al. Facial nerve decompression surgery in patients with temporal bone trauma: analysis of 66 cases. J Trauma. 2011;71(6):1789-93.

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52. Marentette LJ, Valentino J. Traumatic anterior fossa cere­ brospinal fluid fistulae and craniofacial considerations. Otolaryngol Clin North Am. 1991;24:151 63. 53. Singh S, Salib RJ, Oates J. Traumatic fracture of the stapes suprastructure following minor head injury. J Laryngol Otol. 2002;116(6)457 9. 54. Medina M, Di Lella F, Di Trapani G, et al. Cochlear implan­ tation versus auditory brainstem implantation in bilateral total deafness after head trauma: personal experience and review of the literature. Otol Neurotol. 2014;35(2):260 70. 55. Camilleri AE, Toner JG, Howarth KL, et al. Cochlear imp­ lantation following temporal bone fracture. J Laryngol Otol. 1999;113(5):454 7. 56. Simons JP, Whitaker ME, Hirsch BE. Cochlear implanta­ tion in a patient with bilateral temporal bone fractures. Otolaryngol Head Neck Surg. 2005;132(5):809 11. 57. Lyos AT, Marsh MA, Jenkins HA. Progressive hearing loss after transverse temporal bone fracture. Arch Otolaryngol Head Neck Surg. 1995;121(7):795 9. 58. Ghorayeb BY, Yeakley JW, Hall 3rd JW. Unusual complica­ tions of temporal bone fractures. Arch Otolaryngol Head Neck Surg. 1987;113(7):749 53. 59. Yildirim A, Gurelik M, Gumus C. Fracture of skull base with delayed multiple cranial nerve palsies. Pediatr Emerg Care. 2005;21(7):440 42. 60. Souliere Jr. CR, Langman AW. Combined mastoid/middle cranial fossa repair of temporal bone encephalocele. Skull Base Surg. 1998;4:185 9. 61. Majmundar K, Shaw T, Sismanis A. Traumatic cholestea­ toma presenting as a brain abscess: a case report. Otol Neurotol. 2005;26(1):65 7. 62. Sudhoff H, Linthicum Jr FH. Temporal bone fracture and latent meningitis: temporal bone histopathology study of the month. Otol Neurotol. 2003;24(3)521 2. 63. Johnson F, Semaan MT, Megerian CA. Temporal bone fracture: evaluation and management in the modern era. Otolaryngol Clin North Am. 2008;41(3):597 618, x.



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40. Quaranta A, Campobasso G, Piazza F. Facial nerve paraly­ sis in temporal bone fractures: outcomes after late decom­ pression surgery. Acta Otolaryngol. 2001;121(5):652 5. 41. Sofferman RA. Facial nerve injury and decompression. In: Nadol JB, Mckenna MJ (eds), Surgery of the Ear and Temporal Bone, 2nd edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:435 50. 42. Coker NJ, Kendall KA, Jenkins HA, et al. Traumatic intra­ temporal facial nerve injury: management rationale for preservation of function. Otolaryngol Head Neck Surg. 1978;97:262 9. 43. Coker NJ. Management of traumatic injuries to the facial nerve. Otolaryngol Clin North Am. 1991;24:215 27. 44. Bozorg Grayeli A, Mosnier I, Julien N. Long term func­ tional outcome in facial nerve graft by fibrin glue in the temporal bone and cerebellopontine angle. Eur Arch Otorhinolaryngol. 2005;262(5):404 7 45. Nosan DK, Benecke JE Jr, Murr AH. Current perspective on temporal bone trauma. Otolaryngol Head Neck Surg. 1997; 117:67 71. 46. Ulug T, Arif Ulubil S. Management of facial paralysis in temporal bone fractures: a prospective study analyzing 11 operated fractures. Am J Otolaryngol. 2005;26(4):230 38. 47. McGuirt WF Jr., Stool SE. Cerebrospinal fluid fistula: the identification and management in pediatric temporal bone fractures. Laryngoscope. 1995;105(4 Pt 1):359 64. 48. Nishiike S, Miyao Y, Gouda S. Brain herniation into the middle ear following temporal bone fracture. Acta Otola­ ryngol. 2005;125(8):902 5. 49. Leech PJ, Paterson A. Conservative and operative man­ agement for cerebrospinal fluid leakage after closed head injury. Lancet. 1973;1:1013 6. 50. Brodie HA. Prophylactic antibiotics for posttraumatic cere­ brospinal fluid fistulae. A meta analysis. Arch Otolaryngol Head Neck Surg. 1997;123(7):749 52. 51. Andrews JC, Canalis RF. Otogenic pneumocephalus. Laryn­ goscope. 1986;96(5):521 8.

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CHAPTER Vestibular Schwannoma

23

Sean McMenomey, Maja Svrakic

INTRODUCTION Historical Background Vestibular schwannomas were described in the 18th and 19th century, but the first attempt at surgical removal was performed by Charles McBurney in 1891, followed by Sir Charles Balance and Thomas Annandale in the subsequent decade.1,2 These early surgical efforts were largely unsafe and carried up to 78% mortality rates. The stage for modern principles of surgical removal of vestibular schwannomas was set by Harvey Cushing in the early 20th century, who with meticulous hemostasis and gentle dissection brought the mortality rate down to 20% in 1917. He utilized a bilateral suboccipital approach for removal of tumors, allowing for adequate herniation of the cerebellum, which was routinely partially resected in an effort to improve patient survival.3 One should keep in mind that before imaging, in this era, patients presented with late, life-threatening brain stem compressing symptoms from large tumors. It was Cushing’s trainee, Walter Dandy who further refined the technique with a unilateral suboccipital approach, in wide use today.4 The true modern era in surgical resection of vestibular schwannoma was marked by William House in the 1960s, who perfected the translabyrinthine and middle cranial fossa (MCF) approach utilizing the operating microscope and surgical drills.5-7 By the mid-1980s, mortality rates of vestibular schwannomas were consistently under 1%.8 Once mortality was in the background of complications of vestibular schwannoma resection, refinements in technique such as those utilized for facial nerve preservation and, more recently, hearing took precedence.

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Incidence and Epidemiology The most commonly quoted incidence rate of vestibular schwannoma in the United States is 10 per million per year, amounting to almost 3200 newly diagnosed tumors annually.8 This incidence rate is similar to the incidence found in other countries, ranging from 10 to 20 per million people per year.9-15 A recent review of the Denmark patient database over the last four decades reports a significant increase in incidence, from 3 per million per year in 1976, to almost 23 per million per year in 2004 and leveling off at 19 per million per year in 2008.16 The increase in incidence is almost entirely due to improved diagnostic methods, but increased physician and patient symptom awareness certainly play a role. Incidentally discovered vestibular schwannomas, those found in patients who had MRI scans performed for other reasons and either had no symptoms or were not pursuing the cause of their symptoms, may be as high as 2 in 10,000 adults.17 Some older histopathologic studies have found incidental vestibular schwannomas in up to 2.7% of autopsy specimens.18 There appears to be no gender prevalence, although men may have a higher rate of incidentally discovered schwannomas.17The mean age of diagnosis continues to be in the 5th decade of life for sporadic unilateral tumors.16,19 In patients with neurofibromatosis type 2 (NF2), the initial presentation is in the 20s and 30s.20

Etiology and Pathology Vestibular schwannomas arise from the vestibular division of cranial nerve VIII (CN VIII). Their common misnomer

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today owing to earlier diagnoses. The rate of growth rarely exceeds 2 mm per year, and is further discussed in the section on conservative management (“watchful waiting”) of vestibular schwannomas. Measurement of size of vestibular schwannomas is not consistent in the literature. Radiation treatment-based studies report on volumetric dimensions, while studies on surgical treatment or meta-analyses report most frequently the largest axial dimension. The morphologic feature of vestibular schwannomas is distinguished by a spherical component (the cisternal portion) and a tongue-like protrusion into the IAC portion. Thus, calculating a spherical volume from the largest axial diameter (traversing both the cisternal and IAC portion) will overestimate the true volume of tumor. As radiologic diagnostic methods become more sophisticated, a volumetric calculation will likely replace diameter-based estimates. Although there is no universally accepted terminology to describe small versus large tumors, most authors utilize the following classification: 1. Intracanalicular 2. Small: 4 cm (see Fig. 23.4)



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is acoustic neuromas, although the NIH consensus discourages its use. While some groups have shown an equal prevalence in origin between the superior and inferior vestibular nerve (IVN) divisions,21 others report a strong predilection for the IVN.22 Most vestibular nerve schwannomas originate lateral to the glial-schwannian junction.23 The myelin sheath of CN VIII is produced proxi mally by the oligodendroglial cells, and distally by the Schwann cells; the switch in the type of myelin-producing cells can vary, which can account for the variable site of origin of the schwannomas along the vestibular nerve. However, most occur in the vicinity of the vestibular ganglion, where the density of Schwann cells is the highest.24 On gross examination, vestibular schwannomas are yellow-white or yellow-gray heterogeneous masses, with frequent cystic components covered in a smooth and regular surface. Despite the smooth surface that is distinct from the core, there is no true capsule to this tumor. Histo pathologic studies have shown two morphologically distinct cells comprising vestibular schwannomas: Antoni A and Antoni B cells. Antoni A cells are small, densely packed, spindle-shaped cells, while Antoni B cells are pleomorphic, looser, and contain a vacuolated cytoplasm.25,26 The molecular sequence of events that leads to formation of vestibular schwannomas is still under research. The NF2 tumor suppressor gene found on chromosome 22 has been shown to be inactivated in both familial and sporadic cases. The product of the NF2 gene (merlin) regulates Schwann cell division; mutations in both copies are necessary for the phenotype of unregulated growth and resultant vestibular schwannomas.27,28 Estrogen and progesterone hormones,29-31 repeated radiation from diagnostic studies32,33 and even cell phone use34 have all been investigated as environmental factors that may contribute to the development of vestibular schwannomas, although their role is still uncertain.



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CLINICAL MANIFESTATIONS The typical clinical presentation of an early (IAC) vestibular schwannoma consists of symptoms related to CNVIII—

Growth Characteristics

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The stereotypical pattern of growth of vestibular schwannomas consists of an intracanalicular (IAC) component that later expands medially to the cisternal, followed by brain stem compressive and hydrocephalic in its late stages.8 The symptoms of these four classically described stages are progressively more severe, starting with tinnitus or mild hearing loss and progressing to visual loss, lower CN dysfunction, and even death from tonsillar herni ation. The late stages of growth are rarely encountered

Fig. 23.1: Small vestibular schwannoma. Axial Gd-enhanced T1 MRI sequence shows a small left-sided vestibular schwannoma with both a cisternal and intracanalicular component.

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B

Figs. 23.2A and B: Medium-sized vestibular schwannoma. Axial and coronal Gd-enhanced T1 MRI sequence shows a medium rightsided vestibular schwannoma with both a cisternal and intracanalicular component.

Fig. 23.3: Large vestibular schwannoma. Axial Gd-enhanced T1 MRI sequence shows a large left vestibular schwannoma with both a cisternal and intracanalicular component.

hearing loss, tinnitus, and vestibular dysfunction. As the tumor grows medially, in its cisternal stage, hearing loss typically worsens and vertigo progresses to disequilibrium. Further growth with brain stem compression is accompanied with trigeminal symptoms. It is rare to encounter a patient with late brain stem compressive symptoms and hydrocephalus, although large tumors were the norm in the Cushing era, along with visual loss and headaches associated with increased intracranial pressure (ICP). Hearing loss is a symptom found in over 95% of patients. The most likely reason is interruption of the blood supply to the inner ear and cochlear nerve by tumor compression, but also from tumor infiltration of the auditory fibers. The

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Fig. 23.4: Giant vestibular schwannoma. Coronal Gd-enhanced T1 MRI sequence shows a giant right vestibular schwannoma measuring 4.1 cm in the anteroposterior and 3.5 cm in the craniocaudal dimension. Note the resulting hydrocephalus from brain stem and fourth ventricle compression.

hearing loss is typically unilateral and asymmetric, involving preferentially high frequencies. Patients will notice a difficulty with phone use on the affected side. In up to a quarter of patients with vestibular schwannomas, a sudden decrease in hearing occurs, similar to an acute viral infection or vascular occlusion, and can be attributed to idiopathic sudden sensorineural hearing loss (SNHL) only if the presence of a vestibular schwannoma is ruled out with imaging.19,35 The clinician should keep in mind that even in patients who have tumors the sudden loss may recover, and they should be diligent in their search for retro­cochlear pathology.36

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WORKUP Auditory and Vestibular Studies



Conventional pure tone and speech audiometry is the workhorse of diagnostic studies in the initial evaluation of vestibular schwannomas. Classically, patients present with unilateral asymmetric, preferentially high frequency, gradual loss along with decreased SDS that are out of proportion to the pure tone loss. These two cost-effective audiometric tests are a screening tool used to identify those patients who should undergo an MRI imaging study. The advantage of pure tone and speech audiometry is that it is relatively inexpensive and readily available across centers and around the world. The prevalence of vestibular schwannoma in patients with asymmetrical hearing loss has been estimated as high as 7.7%.45-48 There is still no consensus as to what constitutes asymmetric hearing. Methods used include the pure-tone average (PTA) approach (average asymmetry across several specified frequencies), the single-frequency approach (hearing asymmetry is only calculated at one frequency), and multiple frequency pure-tone asymmetry approach (single frequency hearing asymmetries must be present at two or more frequencies and exceed a specified asymmetry criterion). See Table 23.2 for examples of these approaches. The patient’s history should always be considered, especially when hearing loss can be explained by other causes, such as significant head trauma, noise trauma, radiation therapy to the head and neck, chemotherapy, or immunosuppression. These patients may not warrant further workup for retrocochlear pathology. While trigeminal

 



 

 



Normal or symmetric hearing does not rule out a vestibular schwannoma. In fact, up to 15% of patients can have subjectively normal hearing, and up to 4% can be audiometrically normal [stereotactic radiotherapy (SRT) 85%].19,37 Tinnitus is seen in up to 70% of patients, vertigo in 19%, and disequilibrium is reported by up to 70% of patients with large tumors.19,35,37 Other associated symptoms, especially with larger tumors, are a result of trigeminal nerve involvement. Altered facial sensation, most commonly hypoesthesia, can occur in up to 50% of patients with tumor > 2 cm.19 In these patients, the ipsilateral corneal reflex will likely be diminished. Weakness of either the facial or the trigeminal nerve is a rare symptom and occurs with larger tumors. Facial twitching occurs in no >10% of patients.19 If facial nerve function is electroneurographically impaired, the clinician should suspect an alternate diagnosis such as facial nerve neurinomas, malignant tumors of the cerebellopontine angle (CPA), or metastases.38 Large and compressive tumors can manifest with headache and papilledema from resultant hydrocephalus, which occurs in < 4% of patients.19 Lower CN deficits and long tract signs are very rarely seen today. Sudden neurologic deterioration can occur secondary to intratumoral hemorrhage, with acute symptoms of hearing loss, facial spasm or weakness, facial sensory disturbance, hoarseness, and altered mental status.39,40 An emergent surgical intervention, usually with a ventriculostomy, is required. Fortunately, this potentially life-threatening event is seldom encountered. Table 23.1 demonstrates the changing trends in presentation of vestibular schwannomas over the past 100 years.

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Table 23.1: Changing trends in presentation of vestibular schwannoma

Author

Group (year)

N

Hearing loss Tinnitus

Disequilibrium Vertigo

CN V

CN VII

Low CN

Visual symptoms Acute

87%

77% 70%

23% crisis

Cushing41

Hopkins and 30 Harvard (1917)

100%

77%

90% vestibular symptoms

Mathew et al.42

Mayo Clinic (1978)

225

97%

66%

46%

5%

33%

22%

15%

Selesnick et al.43

UCSF (1993)

126

85%

56%

48%

19%

20%

10% 0%

3%

Matthies and Samii35

Hannover (1997)

1,000

95%

63%

61%

61%

17%

17% 3%

2%

Harun et al.44

Hopkins (2012)

1,269

91%

69%

61% dizziness

4%

(CN, cranial nerve).

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Table 23.2: Auditory testing thresholds for further workup of asymmetric SNHL

Author (year) (ref )

Frequencies (kHz)

Threshold criteria

Additional factors

Welling et al.

0.5, 1, 2, 4

≥15 dB

WRS >20% difference Vertigo Sudden SNHL Other CN

Mangham50

PTA (1, 2, 4, 8)

≥5 dB: ABR ≥20 dB: MRI

Ruckenstein et al.51 Cueva47

0.25, 0.5, 1, 2, 4, 8

≥15 dB at 2+ freq

WRS >15% difference

Robinette et al.52

PTA (0.5, 1, 2, 3)

≥15 dB

WRS  30 dB 20 dB at 2 adj freq

Unilateral tinnitus Sudden SNHL

49

(SNHL, sensorineural heart loss; CN, cranial nerve; ABR, auditory brainstem response; PTA, pure-tone average; WRS: word recognition score).

nerve dysfunction is highly suspicious for CPA lesions, fluctuant, low-frequency SNHL associated with aural fullness is rarely concerning for vestibular schwannomas. Patients who develop sudden SNHL, even if it later recovers, should undergo further testing as up to 15% of vestibular schwannomas present in this manner.54,55 What constitutes asymmetric hearing loss that is medically significant continues to vary and is based on clinician’s intuition.56 Asymmetric pure tone and speech audiometry can also be followed up with an auditory brainstem response (ABR). The ABR pattern most specific for presence of a vesti­ bular schwannoma is presence of wave I only, but wave V latency is found in up to 60% of abnormal diagnostic ABRs. In the era of MRIs, the ABR test, once thought of as highly specific and sensitive, has significant false negative and false positive rates. An overall false negative rate may be as high as 15% and up to 33% in IAC tumors.47,57 In larger tumors, however, only 4% of schwannomas had normal ABRs. The false positive rate of ABRs is also surprisingly high, and can exceed 80% in standard, nonsophisticated settings.8 The specificity and sensitivity of ABR, especia­lly in small tumors, can be improved upon with a stacked ABR. Stacked ABRs are composed of neural activity initiated across the whole cochlea and are able to detect by reduction in wave amplitude even IAC tumors with specificity and sensitivity in the 90% range.58

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The role of OAEs is currently limited. OAEs can be used as a risk stratifying method in patients in whom hearing preservation is considered.59-61 Specifically, patients with Class C or D hearing, in whom ABR is undetectable, may suffer from purely retrocochlear conduction but normal cochlear function, which would be detected with good OAEs. Unfortunately, this is not commonly the case, as vestibular schwannomas frequently disrupt cochlear hair cell function, likely by limiting the blood supply to the cochlea.62 Vestibular tests are infrequently used in the diagnosis for vestibular schwannomas. Most commonly this is due to high false positive rates, i.e. many patients who are found to have an abnormal vestibular test will not have a tumor when subjected to an MRI. Although up to 90% of patients with vestibular schwannoma will have an electronystagmography test battery abnormality,63-65 the specificity rate is quite low. Caloric responses can be used to predict the origin of tumor. Since the lateral semicircular canal is sensitive to external warm or cool irrigation, the superior vestibular nerve (SVN) generates the response. Thus, if caloric response is diminished, the SVN is likely affected, and if the caloric response is normal, the IVN could be the nerve of tumor origin. In fact, 98% of SVN tumors show diminished caloric responses, compared to 60% of IVN tumors.65

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NF2 Testing A definitive diagnosis of NF2 requires the presence of bilateral vestibular schwannomas or developing a unila teral vestibular schwannoma by 30 years and a first-degree blood relative with NF2, or the presence of a unilateral vestibular schwannoma and developing at least two of the following conditions known to be associated with NF2: meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacity/juvenile cortical cataract71; see Figures 23.5A and B. Patients with probable NF2 should undergo further evaluation with MRI of the IAC if not already performed, as well as a complete spinal series to evaluate the spine and stage the disease. Genetic counseling should be offered to patients with NF2. Blood screening for the specific mutation of the NF2 gene on chromosome 22 can be performed in patients who have diagnosed NF2, as the defect may be identified in up to 75% of patients, and subsequently used to screen family members. The use of blood screening for patients without a diagnosis of NF2 or with a suspected diagnosis of NF2 is not recommended. ­



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Current diagnostic methods for radiologically detecting vestibular schwannomas almost exclusively rely on MRI. Plain films of the IAC and polytomography are of histori cal interest only. Computed tomography (CT) scans were utilized in the 1970s, and when contrast enhanced can detect tumors >1.5 cm. At present, a contrast-enhanced CT can be of value in patients who cannot undergo an MRI or in the elderly when detecting a small tumor would not change management and the study is done to rule out a larger, brain stem–compressing lesion. The characteristic profile of vestibular schwannomas on gadolinium (Gd)-enhanced MRIs is a brightly enhancing lesion on T1 imaging. Lesions as small as 1 mm can be seen with thin-sectioned sequences targeted to the IAC. In gradient echo T2-weighted high-resolution images such as the constructive interference in the steady state (CISS) sequence, the individual nerves coursing through the IAC appear as hypointense linear structures surrounded by T2 hyperintense cerebrospinal fluid (CSF). Vestibular schwannoma can be seen as a hypointense mass, displacing CSF or distorting adjacent nerves. This sequence is particularly useful in detecting fluid between the lateral end of the vestibular schwannomas and the internal auditory canal fundus, absence of which can have a negative influence on hearing outcome as well as facial nerve function.66 Meningiomas at the CPA can have a similar MRI profile as the vestibular schwannomas. They can be distinguished by their sessile, eccentrically placed base, dural tail, solid consistency (as opposed to cystic), as well as by other morphological factors. Enhancements of the 8th nerve or within the IAC from a viral or immune-mediated neuritis have been reported as false-positive cases of vestibular schwannomas. However, Gd-enhanced MRIs remain a diagnostic gold standard, especially in the age of early detection of small tumors.67,68

A

The major downside of MRIs is their cost and relatively low yield. They can be burdensome in terms of time, expense, and inefficient utilization of health-care capacity. In screening asymmetric hearing loss, the average cost for identifying a positive patient based on MRI was $61,650.69 However, early detection and management of vesti bular schwannomas may result in reduced morbidity, especially since hearing preservation surgery is now a realistic goal if schwannomas are diagnosed and treated before they are >2 cm. Carrier et al. have proposed one way in decreasing the cost of MRI imaging with a focused enhanced sequence.70 Their protocol is of comparable cost to ABRs, and is able to detect small tumors with anatomical detail needed for planning surgical approach.

Imaging Studies



366

B

Figs. 23.5A and B: (A) Definite NF2. (B) Probable NF2 (should evaluate). *Manifestations include meningioma, glioma, schwannoma, or juvenile posterior subcapsular lenticular opacities/juvenile cortical cataract.

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Delayed Diagnosis As MRI imaging became more widespread in the use of ruling out retrocochlear pathology in those patients with asymmetric hearing loss, the delay in diagnosis from onset of symptoms to confirmation of lesion in the CPA became shorter. In 1989, Traquina et al. reported on their vesti­ bular schwannoma patient population who experienced diminished auditory function for over 2 years in 60% of cases, and the mean duration of hearing loss prior to diag­ nosis was over 4 years.72 Clear superiority of the MRI to aid in timely diagnosis was also demonstrated in a Danish study in 1990 where the use of this imaging modality was still limited at the time and a large percentage of tumors were discovered by CT scans, measuring 4 cm in size.73 Reasons for delay may include both patient and physician factors, and are likely to diminish with increased awareness. Because there are no specific clinical findings that clearly distinguish those patients with vestibular schwannomas from other patients with sudden hearing loss,19 an evaluation with ABR or Gd-enhanced MRI for any patient with sudden hearing loss even when hearing normalizes74 is recommended.

MANAGEMENT STRATEGIES Patient Counseling Management of patients with vestibular schwannoma consists of three main strategies: 1. Observation (watchful waiting) 2. Surgical resection 3. Radiation therapy It is especially important that the patient receives counseling with respect to all three of these strategies and that the clinician is familiar with expected outcomes, risks and benefits of observation, surgery, and radiation. This may indeed involve more than one clinician, such as a neurotologist, skull base surgeon, neurosurgeon, and radiation oncologist. Each of the management options is discussed separately below. Choice of management strategy is based on predicted natural course of the tumor and the neurologic sequelae (such as CN deficits and brain stem compression), the ability to either surgically remove the tumor with minimal postoperative complications, or radiate the tumor with least adverse effects. Preservation of hearing, if present at diagnosis, strongly guides management. Patient-specific factors such as age, medical condition, patient’s desire, their ability for follow-up, and social and economical

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support influence treatment options. Finally, the surgeon’s operative skill and familiarity with pitfalls and their avoidance for each surgical approach may dictate the specific intervention chosen (Table 23.3).

Contemporary Treatment Trends and Expected Outcomes A recent meta-analysis of outcomes of all three management strategies compared large studies published since 2004, with a pooled total of over 5,000 patients.75They summarized that observation of patients with vestibular schwannomas offers the least risk, but that growth occurs in 29–54% of the cases and about a half of those patients will require additional treatment. Risks of surgery are avoided with radiation-based treatment, but additional treatment may be required in up to 10% of cases, and radiation-induced risks are not negligible. While surgical resection offers the best control rates and most cytoreductive therapy and very rarely requires additional treatment, it poses risks such as facial nerve neuropathy in about a quarter of the cases. Hearing preservation is comparable in observation and radiation in 3 and 6 years of follow-up, respectively, and can be expected in about half of the cases. With hearing-preservation attempts in microsurgical resection, the chance of hearing preservation falls to about a third of the patients. The most recent patient polling conducted by the Acoustic Neuroma Association in 2008 compiled data from over 2000 respondents, and compared them to the 1983 and 1998 surveys. These are the trends observed by the survey76,77: 1. Tumor size at diagnosis has decreased significantly a. Before 1998, 23.8% tumors were 3 cm was $23,788 compared with $16,143 for radiation treatment. Although the upfront cost of surgery was higher, cumulative cost of radiation and follow-up remained lower only if the rate of tumor progression was 50% in first year

Godefroy et al.

2009

70

4 (mean)

39%

19%

81%

3 years (mean)

Agrawal et al.101

2010

180

10

35%

–

–

2.6 years (mean)

Lloyd et al.114

2010

481

5

50%

–

–

–

Breivik et al.

2012

193

4 (mean)

38%

77%

23%

2 years (mean)

105

111

110

conservative “management”. However, the vast majority of patients opt for active management strategies once the delay has been suspected.

Failure Rates of Conservative Management When talking about failure of conservative management, the focus is mainly on patients who subsequently seek active treatment and not on those patients who are lost to follow-up. Tumor growth was the most important predictor of a change in strategy from conservative to either microsurgical or radiation management.101,103 Reasons for failure of conservative management include most commonly tumor growth, worsening vertigo, progression of hearing loss, and patient decision in absence of changing clinical or radiologic status.85,101 These are summarized in Table 23.6. Evidently, the reasons for pursuing treatment have changed over the past 30 years of follow-up, likely owing to the increase in the use of radiologic studies and the introduction of radiation-based treatments. Table 23.7 summarizes the overall failure rate and the proportion of treatments pursued. Most failures (75–90%) occur within the first 5 years of follow-up.101,105 The patients who changed their treatment

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strategy were significantly more likely to have larger tumors at presentation, tumors located in the CPA, and they were more likely to subsequently display tumor growth at faster rates than individuals who were managed conservatively throughout the study period.101 Incidence of postoperative complications is not higher in patients undergoing secondary surgery than in patients undergoing primary surgery.94,115-119 In other words, delaying the surgical decision does not seem to worsen disease treatment outcomes. Good facial nerve outcome with tumors 3 cm) vesti bular schwannoma, observation rarely plays a role in management, owing mostly to the fact that these tumors are symptomatic, exhibit some brain stem compression, and risk neurologic compromise. In certain cases, however, observation may play a role: 1. When the vestibular schwannoma is in the only hearing ear; in these cases, management is usually undertaken once all hearing is compromised; a contralateral cochlear implant (CI) is an option in these patients126 2. When the patient has bilateral vestibular schwannomas and the one in question is smaller of the two (in cases of NF2); in a recent review of NF2 patients



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Microsurgical Resection



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Microsurgical resection has historically had three prim ary goals in decreasing priority: preserve the patient’s life, maintain the patient’s facial nerve function, and preserve any useful hearing in the operated side. With multiple centers developing standardized resection procedures utilizing operating microscopes, electrophysiological moni toring including CN monitoring, precision instruments, and expertise of neurological and neurosurgical teams, mortality has significantly decreased. Therefore, avoidance of significant postoperative morbidity (CSF leak, meningitis, neurovascular compromise) becomes the focus over simply preserving the patient’s life.128 There are three basic and most commonly utilized approaches in microsurgical removal: retrosigmoid (suboccipital), MCF, and translabyrinthine. The first two ap proaches are hearing-sparing while the last sacrifices any residual hearing. All three approaches involve bony removal via a craniotomy, craniectomy or both, and microdissection of tumor away from the brain, CNS, and adjacent vascular structures. ­



At present, treating clinicians are more often managing small and IAC schwannomas compared to prior decades, which is likely due to improved imaging and increased awareness.121 These smaller tumors are less likely to be symptomatic and do not carry a risk of impending complications. Watchful waiting is a relatively safe approach, with the only significant risk being progression of SNHL. A more proactive approach advocates for early intervention, with the intention of preserving the hearing status at time of diagnosis for these small tumors.122 However, hearing preservation rates for either radiation or microsurgical resection have not been consistently better than the natural history of hearing loss progression with conservatively managed IAC schwannomas. Thus, an increasing number of study groups have advocated for observation-based management.123 In fact, quality-adjusted-life-year totals for all three management strategies in patients with small vestibular schwannomas are highest in patients who undergo a period of observation compared to those who undergo immediate surgery or radiation treatment.124 A recent review of over 3000 patients found that the management of small (2.5 cm

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Table 23.9: Unfavorable preoperative prognostic factors for hearing preservation

Unfavorable preoperative hearing Preservation factor

Diagnostic method

Absent or distorted ABR Even if the hearing level by PTA is good

Auditory function test: ABR

Unaffected caloric response Suggests inferior VN origin (adjacent cochlear nerve in the inferior compartment of the IAC is at risk)136

Vestibular function test: calorics

Deep IAC penetration RSIG approach exposes only proximal two-thirds of IAC; complete resection of tumor in distal one-third requires partial removal of inner ear structures129,137

Imaging: MRI

Tumor size > 2 cm (cisternal component) With the RSIG approach useful hearing may be obtained in 3 cm in size, 84% of which were resected via a TLAB ap­proach, good facial nerve function was preserved in 84% of cases.143 Given that size of tumor significantly affects facial nerve outcome, consideration should be given to subtotal or planned staged resection or postoperative radiation when dealing with tumors >3.5 cm.144 Conversely, entirely IAC tumors (Fig. 23.9) are probably best treated with an MCF or RS approach. In a literature review comparing outcomes of surgical resection of IAC tumors with retrosigmoid versus a MCF approach, the retrosigmoid resection maintained 58% hearing preservation rates (compared to 62% via MCF) but improved facial nerve outcomes and fewer other complications.145 Tumors with a lateral extension into the distal IAC (Fig. 23.10) are not suitable for a retrosigmoid resection and tumors with a large cisternal component have an unfa­ vorable location for a standard MCF resection (see Table 23.8). Clearly, patient priorities (facial nerve function versus hearing function) and surgeon expertise play a large role in selection. Surgical teams with expertise in one over another resection method may preferentially choose the method they have the most favorable results with, irrespective of the reported data from other centers and compiled studies.

Surgical Techniques Much of the operative setup, equipment, surgical site preparation, and postoperative care are common to all

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Fig. 23.9: Vestibular schwannoma with proximal intracanalicular involvement. The constructive interference in steady state gradient-echo T2 MRI sequence shows spinal fluid separating the lateral extension of the right-sided tumor from the cochlea and labyrinth. We chose a hearing-sparing middle cranial fossa approach for this patient.

major surgical approaches to vestibular schwannoma removal; these are summarized in Table 23.10. Surgical removal of vestibular schwannoma carries a risk of intraoperative and postoperative complications, which is the major drawback of surgery over observation or radiation. Discussed below are some basic surgical principles that we follow for all approaches to minimize intraoperative complications and also some not uncommon postoperative complications and suggestions for their avoidance.

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Otology/Neurotology/Skull Base Surgery bipolar cautery; gentle pressure with Gelfoam, pledgets, utilization of thrombin to promote clotting as well as oxidized cellulose (Oxacyl or Surgicel) are safe and effective hemostatic agents.

Surgical Principles The following basic surgical principles are followed for all three approaches: Appropriate patient selection • Careful anatomical review of the preoperative MRI is conducted. Anatomical variants, such as a high riding jugular bulb, may limit dissection extent. • Older patients may have thinner and more adherent dura than younger patients that is more prone to injury, increasing the chance of hematoma or CSF leak; thus approaches that necessitate more dural dissection such as the MCF route may be contraindicated. • As hearing significantly influences the choice of surgical approach, functional hearing should be assessed with a most up-to-date preoperative test.

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Maximizing exposure For any surgery to be performed safely and effectively, good exposure of the surgical field is crucial. The tips on achieving optimum exposure for each of the three major surgical approaches are discussed under the specific app roach; general principles are as follows: • Brain retraction, crucial for RSIG and MCF approaches as well as large tumors, can be facilitated with medications (Mannitol, Lasix) and monitoring for appropriate urinary response; patient positioning with head down and also with hyperventilation in order to lower carbon dioxide to 27–28 mm Hg. • Meticulous hemostasis allows superior visualization of the surgical field; care should be taken when using

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Fig. 23.10: Vestibular schwannoma involving the distal intracanalicular. The constructive interference in steady state gradient-echo T2 MRI sequence shows no spinal fluid separating the lateral extension of the left-sided tumor from the cochlea and labyrinth. We chose a TLAB approach for this patient who presented with class C hearing.

Safe dissection and maximization of functional outcome • Facial nerve and cochlear nerve function monitoring [ABR or cochlear nerve action potential (CNAP)] are routinely used. • Obtain a baseline ABR once the patient is asleep. • Resist blunt dissection and removing the tumor en bloc. • The IAC portion is debulked with CUSA and then sharply dissected off the facial and cochlear nerves that are identified laterally; the IAC portion is removed laterally to medially toward the porus. • The intracranial portion is debulked and the facial and audiovestibular root entry zones are identified on the pons; sharp dissection is utilized to remove the remaining capsule, medially to laterally toward the porus. • Prass probe is used to positively identify the facial nerve and can assist in dissection off of the tumor. • The course of the facial nerve between the brain stem, where it is just slightly inferior to the 8th nerve entry zone, and its entry into the porus where it assumes the anterosuperior location is variable as the tumor can splay the nerve and distort its fibers in almost any direction. The most difficult part of the dissection is removal of the capsule from the thinned facial nerve, just proximal to the anterior edge of the porus acusticus. • Take care to preserve the labyrinthine artery if attempting hearing preservation surgery. • Any maneuver that results in deterioration in the brainstem auditory-evoked responses or abnormal firing of the facial nerve requires immediate cessation to allow recovery. Irrigation with warm saline frequently quiets the facial nerve. Deterioration secondary to surgically induced vasospasm may be managed by local application of papaverine. • Consider subtotal resection if hearing preservation is strongly desired or facial nerve function will be compromised. • Similar principles to those outlined for 7th and 8th CNs should be followed for larger tumors that involve CNs V and IX–XI that can also be monitored intraoperatively; subtotal resection should also be consi dered in cases where lower CNs are involved as their

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Table 23.10: Perioperative considerations

Preoperative

Intraoperative

Postoperative

Anesthesia

Positioning

General endotracheal anesthesia

Operating table turned to 180°

Postoperative care (standard protocol without any complications)

Direct (arterial) blood pressure, heart rate, oxygen saturation, carbon dioxide concentration continuous monitoring

Supine position

Foley catheter for urinary output monitoring Short-acting neuromuscular blockade only (such as with succinylcholine) Medications 24-hour perioperative antibiotics: Ancef or vancomycin for PCN allergy Preoperative IV Decadron Mannitol (20% at 1 g/kg) RSIG and MCF TLAB if large tumor Equipment Operating microscope with assistant head High-speed drill (cutting and diamond burs) Suction-irrigation system

MCF: ipsilateral shoulder elevated; head rotated to 45°opposite tumor; neck slightly extended

Dexamethasone × 48 hours, then taper

TLAB: head rotated to the opposite side of tumor

Analgesia with acetaminophen and codeine

External head fixation per team preference

Postoperative nimodipine can assist in promoting blood flow to the inner ear and maximizing hearing preservation146

Patient secured to bed with three straps and operating table allows inclination in all planes

Antivirals directed at the herpes virus can be used in delayed facial palsy

Pinna

PO day 1

MCF: taped down over earphone with tegaderm

Arterial line, Foley catheter removed

Monopolar and bipolar (micro and macro) cautery

TLAB: prepped into the field and retracted anteriorly

Electrophysiologic monitoring

Shave to at least 1 cm behind incision line

Performed by the EP team

Incision injected with subcutaneous 1% lidocaine with 1:100,000 epinephrine

RSIG and MCF Motor and somatosensory (electrodes in upper and lower extremities) Other cranial nerves (CN V, IX, X, XI) RSIG and TLAB if large tumors

Reglan, Zofran for nausea and vomiting

Preparation

Two suction lines

Earphones for far-field ABR

DVT and PUD prophylaxis

RSIG: head rotated to the opposite side of tumor as far as neck mobility allows; ipsilateral shoulder taped down

RSIG: taped anteriorly over earphone with tegaderm

Facial nerve: direct and transcranial

Admitted to NSICU × 24 hours, then floor care with appropriate clinical neurologic monitoring

Patient mobilized to chair Clear liquid diet, advanced as tolerated PO day 2 JP drain removed from abdomen Patient mobilized to ambulation with assistance

Abdominal site prepared for fat graft

PO day 3

Triple iodine scrub for both the craniotomy and abdominal graft site

Compressive dressing removed, wound inspected

Wound closure

Discharge to home

Bacitracin irrigation and meticulous hemostasis

PO day 10 Stitches removed

Muscle or periosteal flap and subcuta­ neous tissue is approximated in staggered separate layers with interrupted Vicryl stitches Skin is closed with a 3-0 nylon running interlocking stitch Compressive (mastoid) dressing is applied Abdominal closure with interrupted Vicryl, subcutaneous monocryl and JP drain

(RSIG, retrosigmoid; CN, cranial nerve; ABR, auditory brainstem response; TLAB, translabyrinthine; MCF, middle cranial fossa; TLAB, translabyrinthine).

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These are some postoperative complications and tips on minimizing their occurrence as well as recommended management for all surgical approaches to vestibular schwannoma removal: CSF leaks are a relatively common postoperative complication of vestibular schwannoma resection. CSF leak occurs either through the skin at the incision line or the fluid makes its way down the mastoid air cells, the middle ear, and the Eustachian tube manifesting as rhinorrhea or a postnasal drip. The risk of CSF leak extension through the air cells versus the skin incision is slightly higher, with approximately 60% occurring via the mastoid temporal bone air cell route.147-149 These general preventative measures should be undertaken: • Use bone wax or autologous fat with TISSEEL (Fibrin Sealant) to obliterate all fat cells; apical petrous periIAC air cells are a common culprit. • Pressure bandage should be applied postoperatively to minimize wound leaks. • In patients in whom BIH is suspected, consider placing a perioperative lumbar drain. For management of CSF leaks, we employ a graded approach.150 Subcutaneous CSF collections (“pseudomeningoceles”), if not tense or leaking through the incision line, may be amenable to several days of pressure dressing as they typically resolve. Sterile aspiration of the wound collection can also be attempted. Once leaking through the wound, bedside oversowing with mattress sutures, application of pressure dressing and medical measures such as bed rest, head of bed elevation, and avoidance of Valsalva maneuvers can be attempted. Indeed, conservative management has been shown to be successful in up to 53% of cases.151 If unsuccessful, a lumbar drain can be applied for 3–5 days, clamped for 24 hours to test integrity of seal, and removed. More aggressive



Avoiding and Managing Postoperative Complications

management with wound revision may also be indicated; in this case, additional fat, muscle, fascia can be packed and all levels of closure should be carefully inspected and revised as needed. The reported rates of success in the management of CSF leak with lumbar drain placement range from 31% to 83% in the recent literature, and reoperation rates have been reported to range from 21% to 61%.147,149,152-155 CSF rhinorrhea may respond to medical measures as well, acetazolamide can be added, and a lumbar drain can be applied for several days. If revision surgery is needed, a subtotal petrosectomy (in the case of no hearing) with obliteration of the extracanalicular (EAC) and ET block under direct vision with bone wax followed by muscle prevents further leaking. In the case of preserved hearing, an intact wall mastoidectomy can be performed with obstruction of the fossa incudis with fat, muscle or fascia, and TISSEEL. In cases of refractory CSF leaks and where a disturbance in CSF production or absorption is suspected, a permanent (lumbar-peritoneal or ventriculoperitoneal) shunt should be considered. A rare complication of CSF leak, in cases where there is a ball-valve wound effect, is a tension pneumocephalus with signs and symptoms of progressive increase ICP; these should be recognized and treated appropriately. Pneumocephalus can also occur with excessive CSF drainage via placed shunt. A more common complication of CSF leaks is meningitis, discussed below. Postoperative meningitis can be either aseptic (chemical) from meningeal inflammation induced by blood or irritants such as bone dust or cotton wool lint entering the subarachnoid space, or it can be infectious, frequently occurring in conjunction with a CSF leak. Aseptic meningitis is usually associated with headaches, malaise, and a low-grade fever, while infectious meningitis frequently manifests with high fevers, stiff neck, excruciating headache, photophobia, and various degrees of obtundation. Head CT and lumbar puncture or analysis of CSF in cases where LD has been already been placed are diagnostic. In cases of bacterial meningitis, the most common pathogens involved are Staphylococcus species, Enterobacter, and Propionibacterium acnes.156 If the clinical presentation is highly suggestive of bacterial meningitis, intravenous antibiotics with good CSF penetration (vancomycin and ceftriaxone) are initiated immediately as disease progression may be rapid. In addition, corticosteroids and analgesics are used for both bacterial and aseptic meningitis. Because most patients

compromise could significantly affect the patient’s ability to swallow and expose them to a risk of aspiration pneumonia. • Facial nerve function can be compromised by direct traction, blunt trauma, cautery, and rarely transection. Positive probe stimulation at the brainstem root exit zone portends a good prognosis. Lack of response to stimulation at elevated current levels suggests poor recovery.



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Chapter 23: Vestibular Schwannoma presenting with meningitis present with associated CSF leak, management of CSF leak as described earlier is essen­tial. For aseptic meningitis, not only anti-inflammatory corticosteroids but also nonsteroidal anti-inflammatory medications such as Celebrex can be tried. Of note, symptoms may recur after steroid withdrawal. During surgery, avoidance of postoperative meningitis is achieved with the following: • Minimize blood and debris from entering once dura is opened. This is especially important with the retrosigmoid approach as the dura is opened early in the procedure. • Maintain a sterile field and irrigate wound with an anti­biotic solution to minimize wound infections that can lead to bacterial meningitis. Epidural hematoma can be suspected in patients with signs of increased ICP (increased BP, bradycardia, decreased level of consciousness, and/or dilation of pupils). A noncontrast CT scan is indicated in these cases if time allows, but if the onset of symptoms is rapid and the patient becomes unstable, opening the incision for removal of the cranioplasty, abdominal fat, and blood clot at the bedside may be necessary. CPA hematoma is a potentially fatal complication that leads to increased ICP and brain stem compression. These potentially devastating intracranial complications can be minimized with: • Careful observation for bleeding after irrigation of the operative bed after the tumor has been dissected; this is imperative to decrease the likelihood of postoperative compressive CPA hematoma. Anesthesia may be asked to apply Valsalva maneuver or temporarily elevate blood pressure to allow potential bleeders to declare themselves • Careful elevation of the bone flap during craniotomy; some patients may have thinner or more adherent dura • Control postoperative hypertension. Venous infarction from injury to the sigmoid sinus or transverse sinus can occur with TLAB and RSIG app­ roaches during the craniotomy. Some theories proposed to explain dural sinus thrombosis in vestibular schwannoma microsurgery include retraction on the sinus intraoperatively, desiccation of the sinus during tumor resection, and even propagation of bone wax used for control of emissary veins. Venous congestion can be asymptomatic or can manifest with speech disturbance as it will usually affect the temporoparietal region. Rarely, cerebral edema or

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papilledema with progressive vision loss can occur, leading to headaches, visual obscuration, or blindness. The onset of symptoms may range from days to weeks after surgery; Keiper et al. found an onset range from 1 to 35 days postoperatively, with a mean onset of 15.6 days postoperatively.157 Most importantly, signs of venous congestion should be recognized early (CT scan can be used for screening, but a magnetic resonance venography is a more definitive diagnostic tool) and treated with appropriate measures. Treatment of dural sinus thrombosis can range from supportive (steroids, volume repletion, carbonic anhydrase inhibitors) to thrombolytic, including medical anticoagulation, direct endovascular thrombolysis, and even surgical thrombectomy. However, they are best avoided with the following: • Review preoperative films for dominant venous outflow side • Minimize intraoperative mechanical retraction of the sigmoid sinus • Smaller venous tears can be controlled with layering of Gelfoam (thrombin-soaked) and neural patties for gentle pressure. An alternative method is with oxidi­ zed cellulose and gentle bipolar cautery just over the cellulose material • Larger tears may necessitate primary repair with 6-0 Prolene suture with or without addition of muscle; larger tears increase the likelihood of ipsilateral venous outflow compromise • Packing with Surgicel or bone wax should be avoided as this may cause sinus occlusion • Emissary veins can usually be controlled at their root at the sinus with bipolar cautery • Petrosal vein (Dandy’s vein) is frequently ligated in larger tumors; very rarely it can lead to papilledema or cerebellar infarction, but the surgeon should be aware of this potentially devastating complication. The cerebellum, pons, or temporal lobe is vulnerable to traumatic parenchymal injury either from retraction or violation of the pial lining during dissection. Temporal lobe injury from retraction during the MCF approach can be suspected in the case of postoperative seizures, aphasia, and auditory hallucinations. These should be treated medically with ICP-lowering agents and antiseizure medications. The cerebellum can be injured during a RSIG approach and this can manifest with prolonged ataxia and dysmetria. If more significant cerebellar injury has occurred and swelling occurs, surgical evacuation of any associated clots and even resection of the contused cerebellum may be necessary. Approximately one-third of the

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popularized by House for microsurgical exposure of the internal auditory canal in the late 1950s.5 Kawase elaborated on the extended MCF approach in the 1980s with the dissection of the petrous apex, which was used for exposure of aneurysms of the basilar artery and petroclival tumors.161 Today, the MCF approach to the IAC for the purpose of resection of vestibular schwannomas is most suitable for IAC tumors that have a minor CPA component (< 1 cm) and for patients with good hearing [(better than or near 30 dB PTA and 70% word recognition score (WRS)]. Tumors that contact the brain stem are not suitable for the standard MCF approach. Contraindications for a supratentorial craniotomy include age >69 years, ASA (American Society of Anesthesiologists) class >II, and Karnofsky performance scale score  2–2.5 cm this approach should be utilized, as chance of hearing preservation is low. For patients who can tolerate general endotracheal anesthesia, special consideration should be given for patients who have active chronic ear disease, for patients who have the tumor in an only hearing ear and for whom a subtotal resection via a retrosigmoid approach is considered, and for patients who have a high-riding jugular bulb.173 Technical steps Craniotomy: • Incision is planned approximately 3 cm behind pinna (2 fingerbreadths) and is C-shaped. • Anteriorly based periosteal (Palva flap) is made. • Palva flap and skin flap incision should be staggered and approximated with interrupted Vicryl stitches. • Soft tissue is retracted with fish hooks (anteriorly). • Bony landmarks (the EAC anteriorly, spine of Henle, mastoid tip, temporal line) are identified. • Drilling is initiated without the use of a microscope with cutting and then diamond burrs. • Standard landmarks are identified: tegmen plate, sigmoid sinus and sinodural angle, antrum, incus, lateral SCC. • Facial nerve is identified with thinning the bone over it with a 4 diamond burr from its 2nd genu and inferior toward the stylomastoid foramen. • Bony plates over the middle fossa, sigmoid sinus, and posterior fossa are thinned, egg-shelled, and removed. • The larger the tumor, the more the retrosigmoid dura needs to be exposed to allow access, and the further posterior an incision is needed. • Bipolar cautery is used to shrink the dura and facilitate further dural separation from bone and further bone removal. • Labyrinthectomy with preserving the inferior half of the lateral SCC in order to protect the facial nerve. • Inferior extent of dissection: jugular bulb.

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• Cochlear aqueduct is encountered in this location, parallel and inferior to the IAC, which may lead to CSF leakage. IAC: • Ampullae of lateral SCC and superior SCC followed into the vestibule and this marks the entrance of the SVN and the superior and most lateral edge of the IAC. • Troughs are made superiorly and inferiorly around the IAC allowing for 180–270° of removed bone. • Dura over the IAC is incised with a sickle knife. • Tumor is debulked; resection is in lateral to medial direction. Closure: • Remove incus; scar mucosa and place fat followed by TISSEEL into antrum. • Dura over IAC approximated in a “girdle” fashion. • Fat “corks” placed in between the girdle stitches and covered with TISSEEL. • Fat strips packed into the remainder of cavity with TISSEEL.

Specific Issues and Avoiding Pitfalls Maximize exposure: • In cases of anteriorly based sigmoid sinus or a contracted mastoid, full bony removal and decompression of the sigmoid sinus and the temporal lobe may be necessary before further dissection commences. • Inferior dissection should be carried down all the way to the jugular bulb, especially in larger tumors. Maximize outcome: • Counsel patients appropriately with respect to expec­ ted facial nerve outcome: with larger tumors (>3.5cm) about 50% of patients will have a HB1 or 2 1 year postoperatively.144 • Facial nerve should be quickly identified in its descen­ ding portion in the mastoid. • The inferior bony half of the lateral semicircular canal should be left up as long as possible to protect the nerve at its 2nd genu. • If making a trough at the superior aspect of the IAC, avoid drilling in the anterior direction as the labyrinthine portion of the facial nerve. Minimize complications: • Avoid drilling the facial recess; if any facial recess cells are opened, they should be sealed to prevent CSF leak. • The antrum should always be packed off as described above to prevent CSF rhinorrhea.

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CSF Leaks and Cranioplasty after a Translabyrinthine Approach



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Translabyrinthine resection, compared to the other two approaches, leaves the largest cranial defect. The highest rates of reoperation for CSF leak repair have been reported with the translabyrinthine approach.153 Special attention should be given to wound closure and also reconstruction of the bony defect. The rates of CSF leak after translabyrinthine craniotomy have dropped over the past few decades. Some centers perform a cranioplasty with hydroxy apatite cement recontouring with or without titanium mesh, which secures the autologous fat packing; this type of reconstruction has dropped the incidence of postope rative CSF leak to 3 cm in size, hearing preservation was achieved 100% of the time.192 The terminology and extent of the approaches discussed above were been defined previously (Table 23.11).192

Surgical Outcomes When discussing the surgical options with a patient, expec­ted outcomes with respect to preservation of hearing, preservation of facial function, extent of tumor removal and any possible complications as well as options for rehabilitation, need for adjunctive treatment and followup must be thoroughly discussed. This section compares

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Resection

Retrolabyrinthine Semicircular canals remain intact

Translabyrinthine

Horizontal canal and vestibule are ente red; the IAC is opened laterally

Transotic

Complete removal of SCCs and skeleton ization of the facial nerve; EAC obliteration

Transcochlear

Includes transotic, with posterior mobi lization of the facial nerve, removal of cochlea, and exposure of the petrous carotid artery

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(SCC, squamous cell carcinoma; IAC, intracanalicular; EAC, extracanalicular).

the outcomes and complications of the three major surgical approaches with respect to VII and VIII CNs and those related to other factors.

VII and VIII Cranial Nerves



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Hearing preservation: As described above, not all patients are candidates for hearing preservation approaches. Once their adequate candidacy has been determined, they usually undergo either the MCF or the retrosigmoid resection. The success of hearing preservation varies signi ficantly among centers. Also, definition of “success” is not always consistent; the clinician should keep these report ing inconsistencies in mind when reviewing studies. Tables 23.12 A to C outline hearing preservation outcomes in studies published in the past decade. A recent meta-analysis of 49 articles and 998 patients with 6 months to 7 years of follow-up revealed an overall hearing preservation rate of 52% for the RSIG and MCF approach combined.193 Hearing preservation was defined as the percentage of patients who postoperatively had class A or B hearing out of the total number of patients with preoperative class A or B hearing. When separated by approach, 63% out of the total 286 MCF cases and 47% out of the total 702 RSIG cases achieved successful hearing preservation. The advantage that the MCF approach has over the RSIG approach was shown to be significant even when controlling for the size of tumors addressed by the RSIG route. This meta-analysis also confirmed that hearing preservation declines with increasing tumor size. A literature review of only IAC vestibular schwannomas found similar results with an overall hearing preservation rate for the RSIG and MCF approach of 58% and 62%, respectively.145

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Superior and posterior SCCs are removed from the ampullae to the common crus ­

Transcrusal



Approach

There are a few centers that perform comparable number of both MCF and RSIG approaches. More typically, one surgical team prefers one approach over the other and achieves better results with the preferred method. There is large variability between centers in hearing preservation rates for both the RSIG and MCF approach (Tables 23.12A and 23.12B). Interestingly, within one center, when tumors are controlled for size, data show similar hearing outcomes (Table 23.12C). This is probably due to reporting bias.132 With MCF resections, the long-term results of hearing preservation are good even after 5 years. One study showed that the initial postoperative class A hearing was preserved in class A or B in 95% of the cases at the conclusion of the 5-year follow-up; in another, WRS class I hearing (SDS>70%) was maintained in 23 (88%) of 26 patients with >5 years of follow-up.194,195 Intraoperative monitoring of hearing function with ABR or CNAP during vestibular schwannoma surgery is routinely performed by many surgeons. A review from Stanford found that monitoring by CNAP is significantly associated with a higher chance of hearing preservation,196 while monitoring by ABR did not have a positive influence on hearing preservation results. Superiority of direct (CNAP) 8th nerve monitoring was also demons trated by Danner et al. hearing was preserved in 71% of patients with tumors 1 cm or less and in 32% of patients with tumors between 1 and 2.5 cm, compared to 41% and 10% when ABR was used for the same size matched tumors.197 Another intraoperative predictor of hearing outcome may be severity of adhesion of the tumor to the 8th nerve; tumors with severe adhesions may be associated with a hearing preservation rate of 50%

196

200

Gjuric et al.201 Woodson et al.

195

Table 23.12B: Hearing preservation outcomes in recent studies: RSIG

Author (ref )

Group (year)

No patients

Hearing outcome (tumor size)

Mazzoni et al.202

Ospedali Riuniti (2000)

64

48% A/B

Kaylie et al.

Oregon (2001)

44

29% A/B (6 mos) or likely to not be complete, and the patient is at risk of corneal injury, a gold weight or lid tightening procedures should be considered. If recovery is not full, but the patient has some mimetic function, facial nerve exercises are a part of the rehabilitative program. Electrodiagnostic tests can aid with prog nosis. In most cases of questionable or incomplete recovery, patients should be referred to facial plastic surgeons who specialize in facial nerve and facial reanimation. Botox injections to the contralateral side may aid in relaxing the contralateral face and improving symmetry. Hypoglossal to facial nerve grafts may be considered after 18 months to 2 years of loss of activity, as well as static procedures or microvascular grafts in cases of severe asymmetry or disability.

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Options are as with any other cause of single-sided deafness, including a CROS aid, bone-anchored hearing device (BAHA or SoundBite), preferential positioning, and raised awareness for noise and toxin protection for the uninvolved ear. While cochlear implants (CIs) are now playing a role in other patients with SSD, in the context of vestibular schwannomas, they are considered only for NF2 patients with bilateral tumors and intact nerves (such as after radiation). A CI, however, may play a role in patients who have a vestibular schwannoma in the only hearing ear, and should be considered in the nontumor ear side, and placed prior to vestibular schwannoma intervention. This should be carefully planned, as current CIs require removal of the magnet to be compatible with MRI scans.

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Hearing Aids and Options for Single-Sided Deafness

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Hearing loss is the most frequent presenting symptom of vestibular schwannomas. It is also a risk of all three management approaches: watchful waiting, microsurgery and radiation treatment. It is likely that the patient will at some point in time be faced with considering rehabilitative options of single-sided deafness.

Dizziness can have a significant impact on the patient’s QOL. Vestibular symptoms may occur as a part of the natural progression of tumor growth, and patients should be appropriately counseled when opting for the wait and scan strategy. They are also common in patients who undergo radiation treatment. With respect to surgical resection, patients usually experience acute vertigo after a TLAB approach, which subsides with time as compensation with the contralateral vestibular system occurs. Most advocate for a complete transection of the vesti bular nerves during tumor removal in RSIG and MCF approaches. However, Mann et al. have found that preserving the uninvolved division of the vestibular nerve accelerates vestibular compensation in the early postoperative period; this effect was not significant 6 months after surgery.38 In a study by Feigl et al., 43.5% of patients complained of dizziness prior to tumor removal and 77.2% experienced dizziness after RSIG approach to tumor resection.233 Their study shows that dizziness has a negative effect on the course of recovery, and they advocate for administration of antiemetics preoperatively in addition to widely utilized postoperative therapies. Preoperative status of the contralateral vestibular system affects the time and extent of compensation after surgical resection of tumor as well as after radiation treatment. Presence of contralateral Meniere disease, labyrinthitis, or vestibular neuritis will likely result in poorer outcomes and longer recovery time. For symptomatic management, vestibular rehabilitative therapy plays an important role in patients with vestibular schwan nomas, either as a part of postoperative, postradiation or

Auditory Rehabilitation

Vestibular Rehabilitation

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Chapter 23: Vestibular Schwannoma wait-and-scan management strategy. Another option in patients with severe symptoms is ablation of the ipsilateral vesti­bular system with intratympanic gentamicin, even at the expense of hearing. In postradiation cases, or cases where the transection of vestibular nerves was not complete and even in patients who opt to not undergo tumor removal, an ipsilateral labyrinthectomy can be considered.

NF2-ASSOCIATED VESTIBULAR SCHWANNOMAS Background Approximately 5% of patients who have a vestibular schwannoma have Neurofibromatosis 2 (NF2). NF2 vesti­ bular schwannomas are histologically distinct from sporadic vestibular schwan­nomas.359 NF2 is a rare autosomal dominant syndrome charac­ terized by bilateral vestibular schwannomas, multiple meningiomas, CN and spinal tumors, and eye abnormalities. The incidence is estimated to be 1 in 33,000 to 1 in 87,000 live births.360,361 NF2 is distinctly genetically and clinically separate from NF1; NF1 has been localized to chromosome 17 and NF2 to chromosome 22. NF1 is a multi­ system disorder in which some features may be present at birth and others are age-related manifestations (among them café au lait spots, optic gliomas, neurofibromas, iris hamartomas, etc.). NF1 and NF2 can be distinguished by a careful examination and detailed history of the patient’s symptoms. The most common presenting symptom of a patient with NF2 is a neurologic complaint (found in 17.5% patients), followed by an appearance of a skin tumor (11.7% patients) and vision loss (10.7%); up to 10.7% of patients are asymptomatic at time of diagnosis.362 Despite these trends, there is significant heterogeneity in presentation. While some patients may have a very mild form with small vestibular schwannomas manifesting later in life, in others the disease can be aggressive, disseminated and locally invasive, and may require a multispecialist team approach.

Management The treatment options for NF2 patients who have bilateral vestibular schwannomas depend on the patient’s clinical presentation and tumor size. Loss of useful hearing, the status of other intracranial tumors, presence of brainstem compression, or hydrocephalus must all be considered when discussing the management options.

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Watchful Waiting Watchful waiting with serial imaging is the most common management option utilized in patients with NF2, be it in the setting of a small tumor in the only-hearing ear or of bilateral tumors too large for hearing preservation attempts. As with sporadic vestibular schwannomas, an MRI is performed 6 months after the diagnosis and then annually. Microsurgical removal should be considered if there is a change in clinical status (brainstem compression, progression to unserviceable hearing) or if the tumor significantly enlarges. There have even been reports of patients in whom the contralateral tumor decreased in size after surgical removal of the opposite-side schwannoma.363

Medical Management Medical management of NF2-associated vestibular sch­ wannoma is still early in development. Therapy in the form of antibodies targeted against VEGF (bevacizumab) may hold some promise not only in the reduction in size of vestibular schwannomas but also in improvement in hearing.364,365 Other clinical trials are investigating lapatinib and rapamycin to stop the growth of NF2 vestibular schwannomas.366 Erlotinib held initial promise in a case report but failed to show benefit in a larger study, and in fact many patients suffered side effects.367,368 Although early results of drug therapies have been promising, longterm studies are still needed to demonstrate benefit.

Surgical Management Hearing preservation: Hearing preservation in patients with NF2-associated vestibular schwannoma is a reasonable option for those patients who have bilateral tumors smaller than 2 cm and good hearing (class A or B). The tumor that should be resected first is on the side of the worse hearing ear or if it is the larger of the two. If hearing preservation is successful, then the contralateral tumor may be addressed 6 months later. Hearing preservation results in patients with NF2 seem to be worse compared to patients who have unilateral sporadic tumors.251 In one series, 67% of patients qualified for hearing preservation.369 The MCF approach offers the best results in hearing preservation for patients with NF2-associated vestibular schwannomas, with the highest preservation rates reaching 50%.370,371 Therefore, microsurgical removal via the MCF approach should be offered to patients who qualify, including children, and potentially preserve hearing in both ears.

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Radiation treatment: From the reported results on GKRS for NF2-associated vestibular schwannoma, it appears that GKRS is less effective in treating tumors secondary to NF2 compared to sporadic cases.279,280, 373-375 In the largest study of 122 tumors, the average marginal dose was 15 Gy, higher than what is used for unilateral cases, and clinical tumor control rate was 79% at 4 years of follow-up.375 Twenty percent of the tumors were treated with one or more prior microsurgical resections. The majority of patients were treated for documented tumor growth; other indications for GKRS in this population included a rapid deterioration in hearing, tumor near 3 cm in size, or planned adjuvant therapy for significant residual tumor



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Nonhearing preservation: Most patients with NF2 vesti bular schwannoma present with tumors that are too large to be considered for hearing preservation. Therefore, the most common microsurgical removal is achieved with the TLAB or RSIG approach. If there is brainstem compression, even in cases where patients still have some hearing, the TLAB or RSIG craniotomy should be performed as they allow safest and complete tumor removal. Of the two, the TLAB approach is preferred as the RSIG may not allow for dissection of the most lateral aspect of the IAC, and thus carries a slightly higher risk of recurrence.

Auditory rehabilitation: Auditory rehabilitation in patients with NF2 leaves two basic options: (1) for patients with smaller tumors (2.5 cm), an ABI can be placed at the time of microsurgical resection (TLAB or RSIG approach).280,379,380 Prior to placing a CI, electrical promontory stimulation can help determine the presence and functionality of the cochlear nerve. In the group of 10 patients with NF2-associated tumors who underwent SRS, hearing outcomes after CIs were favorable.381 In the United States, the ABI, a device intended to stimulate the dorsal cochlear nucleus at the brainstem, is FDA-approved for use in individuals with NF2 older than 2 years of age. The ABI can be placed with the first tumor removal as a “sleeper” even when useful hearing may still be present on the contralateral ear, and then be activated at a later date. With progression of contra lateral disease, a second ABI can be placed at removal of the second tumor, offering the advantage of bilateral ABIs. Most patients with NF2-associated tumors have achieved enhanced communication skills with ABIs. An important consideration in patients with NF2 is the need for frequent surveillance MRIs, and thus the magnet should be removed from the receiver stimulator when implanting either CI or ABI.

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Prophylactic MCF and IAC decompression: In patients whose tumors are observed and suffer some progression of hearing loss, a decompression of the IAC via the MCF approach can be considered as a prophylactic measure against complete hearing deficit. Not only can stabilization of current level of hearing occur, but improvement in hearing has been documented as well.372 For this specific indication, the tumor itself is not removed as this may increase the risk of hearing loss. In a review of 49 patients who underwent IAC decompression via a MCF cranio tomy, hearing preservation was successful in 90% in the immediate postoperative period and approximately 75% 1 year later. While the advantage may be only an average of an extra 2 years of hearing, some patients continue to have auditory function up to 10 years later.372

after microsurgery. The serviceable hearing preservation rate in those patients who qualified was 22% at 4 years of follow-up, lower than the results seen with sporadic tumors. Mathieu et al. found in their series hearing preservation rates of 73%, 59% and 48% at 1-, 2- and 5-year follow-up, respectively, indicating that the radiation effects continue long after radiation treatment.279 Patients and their families should be counseled appropriately with respect to their expectations. An important and concerning consideration in this population is that radiation of NF2-associated vestibular schwannoma may lead to malignant tumor transformation, especially because of an already defective tumor suppressor gene.376 Of the 14 cases reported with histologically verified intracranial malignancy arising in a stereotactically irradiated field, four were patients with NF2.377 At least 5 of 106 patients with NF2 who underwent radiotherapy developed radiation-induced malignancies, and nearly 50% of reports of malignant degeneration occur in the context of NF2.376,378





In patients with NF2, the retrosigmoid approach to vestibular schwannoma removal is particularly risky for hearing preservation, as the cochlear fibers are dispersed throughout the tumor, unlike what is typically seen in unilateral vestibular schwannomas. This anatomical relationship is likely the reason why even partial tumor removal of NF2-associated schwannomas risks hearing.366



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Chapter 23: Vestibular Schwannoma

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336. Charabi S, et al. Cystic vestibular schwannoma—clinical and experimental studies. Acta Otolaryngol Suppl. 2000; 543:11-3. 337. Benech F, et al. Cystic versus solid vestibular schwannomas: a series of 80 grade III-IV patients. Neurosurg Rev. 2005;28(3):209-13. 338. Pendl G, et al. Acoustic neurinomas with macrocysts treated with Gamma Knife radiosurgery. Stereotact Funct Neurosurg. 1996;66 Suppl 1:103-11. 339. Delsanti C, Regis J. Cystic vestibular schwannomas. Neurochirurgie. 2004;50(2-3 Pt 2):401-6. 340. Pollock BE, et al. Vestibular schwannoma management. Part II. Failed radiosurgery and the role of delayed microsurgery. J Neurosurg. 1998;89(6):949-55. 341. Pollock BE, Link MJ. Vestibular schwannoma radiosurgery after previous surgical resection or stereotactic radiosurgery. Prog Neurol Surg. 2008;21:163-8. 342. Pollock BE, et al. Vestibular schwannoma management. Part I. Failed microsurgery and the role of delayed stereotactic radiosurgery. J Neurosurg. 1998;89(6):944-8. 343. Unger F, et al. Radiosurgery of residual and recurrent vestibular schwannomas. Acta Neurochir (Wien). 2002;144(7):671-6; discussion 676-7. 344. van de Langenberg R, et al. Management of large vestibular schwannoma. Part I. Planned subtotal resection followed by Gamma Knife surgery: radiological and clinical aspects. J Neurosurg. 2011;115(5):875-84. 345. Yomo S, et al. Repeat gamma knife surgery for regrowth of vestibular schwannomas. Neurosurgery. 2009;64(1):48-54; discussion 54-5. 346. Dewan S, Noren G. Retreatment of vestibular schwannomas with Gamma Knife surgery. J Neurosurg. 2008;109 Suppl:144-8. 347. Husseini ST, Piccirillo E, Sanna M. On “malignant transformation of acoustic neuroma/vestibular schwannoma 10 years after gamma knife stereotactic radiosurgery” (skull base 2010;20:381-388). Skull Base. 2011;21(2):135-8. 348. Demetriades AK, et al. Malignant transformation of acoustic neuroma/vestibular schwannoma 10 years after gamma knife stereotactic radiosurgery. Skull Base. 2010;20(5): 381-7. 349. Schmitt WR, et al. Radiation-induced sarcoma in a large vestibular schwannoma following stereotactic radiosurgery: case report. Neurosurgery. 2011;68(3):E840-6; discussion E846. 350. Yang T, et al. A case of high-grade undifferentiated sarcoma after surgical resection and stereotactic radiosurgery of a vestibular schwannoma. Skull Base. 2010;20(3):179-83. 351. Markou K, et al. Unique case of malignant transformation of a vestibular schwannoma after fractionated radiotherapy. Am J Otolaryngol. 2012;33(1):168-73. 352. Kaylie DM, McMenomey SO. Microsurgery vs gamma knife radiosurgery for the treatment of vestibular schwannomas. Arch Otolaryngol Head Neck Surg. 2003;129(8):903-6. 353. Pollock BE. Vestibular schwannoma management: an evidence-based comparison of stereotactic radiosurgery and microsurgical resection. Prog Neurol Surg. 2008;21:222-7.

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354. Tos M, et al. Causes of facial nerve paresis after translabyrinthine surgery for acoustic neuroma. Ann Otol Rhinol Laryngol. 1992;101(10):821-6. 355. Carlson ML, et al. The anatomically intact but electrically unresponsive facial nerve in vestibular schwannoma surgery. Neurosurgery. 2012;71(6):1125-30. 356. Franco-Vidal V, et al. Delayed facial paralysis after vestibular schwannoma surgery: role of herpes viruses reactivation—our experience in eight cases. Otol Neurotol. 2004; 25(5):805-10. 357. Sampath P, et al. Late-onset facial nerve degeneration after vestibular schwannoma surgery: incidence, putative mechanisms, and prevention. Neurosurg Focus. 1998;5(3):e6. 358. Strauss C, et al. Preservation of facial nerve function after postoperative vasoactive treatment in vestibular schwannoma surgery. Neurosurgery. 2006;59(3):577-84; discussion 577-84. 359. Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofibromatosis 2 and in unilateral cases. J Neuropathol Exp Neurol. 1993;52(2):106-13. 360. Evans DG, et al. Birth incidence and prevalence of tumorprone syndromes: estimates from a UK family genetic regis­ter service. Am J Med Genet A. 2010;152A(2):327-32. 361. Antinheimo J, et al. Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas. Neurology. 2000;54(1):71-6. 362. Brackmann DE, Shelton C, Arriaga MA. Otologic surgery, 3rd edition. Philadelphia, PA: Saunders/Elsevier; 2010. xxi, 831p. 363. von Eckardstein KL, et al. Spontaneous regression of vestibular schwannomas after resection of contralateral tumor in neurofibromatosis Type 2. J Neurosurg. 2010;112(1): 158-62. 364. Plotkin SR, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361(4):358-67. 365. Wong HK, et al. Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. Cancer Res. 2010;70(9): 3483-93. 366. Hoa M, Slattery WH, 3rd. Neurofibromatosis 2. Otolaryngol Clin North Am. 2012;45(2):315-32, viii. 367. Plotkin SR, et al. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol. 2010; 31(7):1135-43. 368. Plotkin SR, et al. Audiologic and radiographic response of NF2-related vestibular schwannoma to erlotinib therapy. Nat Clin Pract Oncol. 2008;5(8):487-91. 369. Doyle KJ, Shelton C. Hearing preservation in bilateral acoustic neuroma surgery. Am J Otol. 1993;14(6):562-5. 370. Slattery WH, 3rd, Brackmann DE, Hitselberger W. Hearing preservation in neurofibromatosis type 2. Am J Otol. 1998; 19(5):638-43. 371. Slattery WH, 3rd, et al. Hearing preservation surgery for neurofibromatosis Type 2-related vestibular schwannoma in pediatric patients. J Neurosurg. 2007;106(4 Suppl): 255-60.

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Chapter 23: Vestibular Schwannoma 372. Slattery WH, et al. Middle fossa decompression for hearing preservation: a review of institutional results and indications. Otol Neurotol. 2011;32(6):1017-24. 373. Kida Y, et al. Radiosurgery for bilateral neurinomas asso­ ciated with neurofibromatosis type 2. Surg Neurol. 2000; 53(4):383-89; discussion 389-90. 374. Roche PH, et al. Neurofibromatosis type 2. Preliminary results of gamma knife radiosurgery of vestibular schwannomas. Neurochirurgie. 2000;46(4):339-53; discussion 354. 375. Rowe JG, et al. Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofibromatosis. J Neurol Neurosurg Psychiatry. 2003;74(9):1288-93. 376. Baser ME, et al. Neurofibromatosis 2, radiosurgery and malignant nervous system tumours. Br J Cancer. 2000; 82(4):998.

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377. Carlson ML, et al. Radiation-induced rhabdomyosarcoma of the brainstem in a patient with neurofibromatosis type 2. J Neurosurg.2010;112(1):81-7. 378. Evans DG, et al. Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet. 2006;43(4):289-94. 379. Lustig LR, et al. Cochlear implantation in patients with neurofibromatosis type 2 and bilateral vestibular schwannoma. Otol Neurotol. 2006;27(4):512-8. 380. Ahsan S, et al. Cochlear implantation concurrent with translabyrinthine acoustic neuroma resection. Laryngoscope. 2003;113(3):472-4. 381. Trotter MI, Briggs RJ. Cochlear implantation in neurofibromatosis type 2 after radiation therapy. Otol Neurotol. 2010;31(2):216-9.

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Meningioma and Other Non-vestibular Schwannoma Tumors of the CPA

CHAPTER

24

Adam A Master, Maura K Cosetti

INTRODUCTION The term cerebellopontine angle (CPA) refers to the intra­ cranial space bounded by the cerebellum, pons, and the petrous portion of the temporal bone. Traversed by a large number of neurovascular structures, tumors in this region can be diverse in clinical presentation and subject to a variety of available treatment options. Although the most common CPA tumor is a vestibular schwannoma (VS), a benign growth of the vestibular portion of the eighth crani­ al nerve (CN VIII), a long list of potential pathologies may be found in this region. VSs account for approximately 90% of pathology in the CPA, while meningiomas, epider­ moids, facial schwannomas, and other more rare lesions comprise the remaining 10% of tumors (Table 24.1). This chapter will discuss the clinical findings and audioves­ tibular evaluation of non-VS pathology of the CPA, as well as the pathogenesis, imaging, and treatment specific to CPA meningiomas, epidermoids, arachnoid cysts, facial schwannomas, hemangiomas, metastatic disease, and intra-axial lesions.

CPA ANATOMY A thorough understanding of CPA anatomy provides the foundation on which to base a discussion of the diverse pathology of this intracranial area. Situated in the poste­ rior fossa, the CPA is bounded anteriorly by the petrous portion of the temporal bone and the lateral clivus and posteriorly by the flocculus and the petrosal surface of the cerebellum (Fig. 24.1). The lateral aspect of the tento­ rium marks the superior border, while the inferior extent app­roaches the lateral surface of the medulla. Laterally,

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Table 24.1: Differential diagnosis of cerebellopontine angle pathology

Common lesions (in order of decreasing frequency) Vestibular schwannoma Meningioma Epidermoid Facial nerve schwannoma Arachnoid cyst Uncommon lesions Hemangioma Lipoma Dermoid Teratoma Metastatic disease Intra-axial lesions Glioma Medulloblastoma Choroid plexus papillomas Ependymomas Hemangioblastoma

the space is bounded by the internal auditory meatus (or porus acusticus) along with the entirety of the posterior petrous temporal bone. The pons, as well as the begin­ ning of the contralateral CPA cistern, represents the medial extent. The apex of the CPA abuts the lateral recess of the fourth ventricle and approximates the region of the pontomedullary junction where the cochlear and vestibu­ lar divisions of CN VIII enter the brain stem. The choroid plexus of the fourth ventricle may occasionally protrude through the foramen of Luschka into this area.

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Fig. 24.1: Anatomy of the cerebellopontine angle. (5, cranial nerve 5 (trigeminal); 7, cranial nerve 7 (facial); 8, cranial nerve 8 (vestibulocochlear); 9, cranial nerve 9 (glossopharyngeal); 10, cranial nerve 10 (vagus); 11, cranial nerve 11 (spinal accessory); AICA, anterior inferior cerebellar artery; BS, brainstem; Co, cochlea; ES, endolymphatic sac; ED, endolymphatic duct (also known as the vestibular acqueduct); IV, inferior vestibular nerve; JB, jugular bulb; JV, jugular vein; LSCC, lateral semicircular canal; PICA, posterior inferior cerebellar artery; PSCC, posterior semicircular canal; SCA, superior cerebellar artery; SSCC, superior semicircular canal; SS, sigmoid sinus; SV, superior vestibular nerve).

The CPA is lined by meninges, filled with cerebrospi­ nal fluid (CSF), and traversed by a number of neurovas­ cular structures entering and exiting the skull base. The vestibulo­cochlear (CN VIII) and facial (CN VII) nerves are the core neural structures within the CPA. With respect to vascular structures, the CPA includes the anterior and posterior inferior cerebellar arteries (AICA and PICA, respectively) and their branches (including the important internal auditory artery), as well as the venous drainage of the cerebellum, pons, and medulla.

CLINICAL FINDINGS Symptoms and signs of CPA tumors are directly related to the neurovascular anatomy of the skull base region they involve. As mentioned above, the primary CN VII and VIII course through the CPA cistern as they travel from their origin in the brain stem to the fundus of the internal audi­ tory canal (IAC). Tumors extending medially can involve the trigeminal nerve, CN V, while those extending inferiorly can abut the lower CNs (glossopharyngeal, vagus, accessory and hypoglossal, CN IX–XII, respectively). Although the

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list of symptoms caused by CPA pathology can be diverse, it is not surprising that the most common are hearing loss, imbalance/disequilibrium, and tinnitus. Symptoms rela­ ted to the facial and trigeminal nerves, specifically facial paresis, paralysis, spasm, pain and paresthesias, as well as cerebellar symptoms, such as ataxia, are also frequent.1,2 Unsurprisingly, complaints of papilledema, diplopia, abdu­ cens palsy, which are related to structures anatomically distant from the CPA (i.e. the optic and oculomotor nerves), are less common. Similarly, symptoms related to lower CN dysfunction, such as dysarthria, hoarseness, and dyspha­ gia, are less also frequent. CPA tumors can induce symp­ toms indicative of increased intracranial pressure or mass effect, including headache, hemiparesis, and dementia. Often, due to the nonspecific nature of some complaints and the complexity of the anatomic structures in this region, many of the above symptoms (i.e. imbalance) may have a multifactorial etiology. Overall, CPA tumors may present with a variety of complaints and they may also remain asymptomatic. For this reason, it is not possible to diagnosis CPA patho­ logy using symptomatology alone. Following identification of a CPA mass, it is similarly impossible to differentiate between tumor pathology on the basis of presenting symp­ toms. Clinical findings unique to various pathologies will be discussed in more detail below.

AUDIOVESTIBULAR AND FACIAL NERVE TESTING Audiometry Prior to the advent of sophisticated imaging technology such as magnetic resonance imaging (MRI; discussed at length in an upcoming section), audiovestibular testing played a larger role in the diagnosis of CPA pathology. Unsurprisingly, the vast majority of studies on audiome­tric evaluation of CPA tumors included patients with VS. There are significantly less data available on the audiome­tric presentation of non-VS tumors. Available evidence sug­ gests that meningiomas and other non-VS CPA pathology do not have unique audiometric features distinguishing them from VS. Importantly, however, while audiometry currently functions as a useful (not mandatory) adjunct in the diagnosis of CPA pathology, it is a crucial and required element in treatment decision making and should be per­ formed in all non-VS tumors. Mechanisms of damage to the audiovestibular system from a non-VS CPA tumor mimic those from a VS, including direct compression on CN VIII or the brain stem nuclei, neural, or cochlear ischemia from disrupted

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Chapter 24: Meningioma and Other Non-vestibular Schwannoma Tumors of the CPA arte­rial supply or impaired venous drainage, biochemical alteration of the inner ear, hair cell degeneration second­ ary to neuronal loss within CN VIII (i.e. deafferentation), as well as direct or indirect effects from primary cortical or cerebellar pathology.3 Although not independently diagnostic of a CPA lesion, auditory brain stem response testing (ABR) is the most useful audiometric test for diagnosis of CPA patho­ logy.4 For VS, it has been shown to have a sensitivity of 100% and a specificity of 61.9%.5 This surpasses that of behavioral audiometry, including various “site of lesions” tests indicative of retrocochlear pathology such as reduced word discrimination, abnormal acoustic reflex thresholds, and presence of acoustic reflex decay. Data suggest that sensitivity and specificity of ABR in diagnosis of non-VS tumors of the CPA is less than for VS; as many as 15% of non-VS tumors may have normal ABRs. 6 At present, use of electrophysiologic studies such as ABR, stacked ABR, auditory steady-state response testing (ASSR), and otoacoustic emissions in the diagnosis and management of non-VS lesions is variable and physician or institution dependent. As the sensitivity and specificity of MRI has surpassed that of available audiometric testing, routine use of these tests for diagnosis is not advocated.7,8 Following diagnosis, the presence or degree of hear­ ing loss is an important factor in CPA tumor management and may specifically impact the timing, candidacy, or suc­ cess of various treatment options (additional discussion in the treatment section, below). Behavioral audiometry (including pure tone air and bone levels and speech dis­ crimination testing) remains the gold standard for func­ tional hearing assessment and should be performed in all patients with known or suspected CPA tumors.

Vestibular Testing Vestibular testing, including video- and electronystagmog­ raphy, is used inconsistently in the diagnosis and manage­ ment of CPA tumors. A reduction in caloric responses has been documented in two-third of patients with CPA meningiomas; however, the findings are nonspecific.9 In VS management, vestibular testing may be useful in dis­ tinguishing between tumors arising from the inferior or superior vestibular nerve. These data may occasionally be useful in counseling patients on tumor management, such as the opportunity for hearing preservation surgery. It is not widely applied to non-VS tumors of the CPA.

Electroneuronography Electroneuronography (ENoG) assesses facial muscle response to maximal bipolar stimulation at the stylomastoid

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foramen and has also been inconsistently applied in diagnosis of these tumors. Measurements obtained give indirect information about the quantity of synchronous functional motor units of the facial nerve (FN), includ­ ing the motor axon, end plate, and muscle fibers. These measure­ments may suggest reduced function even when not clinically evident. Overall, ENoG testing is of limited value in slow-growing, progressive lesions in which the motor units may experience partial degeneration and regeneration. 10 For these reasons, it is not commonly employed in the diagnosis or management of CPA lesions, including facial schwannomas.

MENINGIOMAS Pathogenesis Meningiomas are the most common extra-axial, intra­ cranial tumor pathology; however, they account for only 3–12% of CPA tumors. Overall, the CPA ranks 8th in in­ tracranial location, although it represents the most com­ mon location in the posterior fossa. Meningiomas arise from meningothelial cells, specifically the arachnoid cap cells located in the tips of arachnoid villi that are respon­ sible for CSF absorption. Within the cranial vault, menin­ giomas are found along skull base foramina, dural sinuses, and large tributary veins. Other locations for meningioma growth in the posterior fossa include the clival and petro­ clival region, Meckel’s cave, the jugular foramen, IAC, and foramen magnum. Epidemiologically, meningiomas have an overall an­nual incidence of approximately 6 per 100,000 individuals. In symptomatic patients, however, the overall incidence is less, estimated at 2–3 per 100,000. Due to their benign pathology and overall slow growth, meningiomas repre­ sent >30% of incidental brain tumors found postmortem. Meningioma incidence increases with age, peaking in the 6th and 7th decades, and is rare in children (account­ ing for  95% of meningiomas are sporadic, the remainder are associ­ ated with a variety of hereditary syndromes, including NF2 as well as Werner’s, Gorlin’s, and Cowden’s syndromes. NF2 is an autosomal dominant disease characterized by the development of multiple intracranial and spinal tumors, specifically bilateral VS, meningiomas, and ependy­ momas. Between 30% and 50% of NF2 patients develop meningiomas. It was the initial cytogenetic analysis of

meningiomas samples that led to the identification of the NF2 gene, Merlin. Located on the long arm of chromo­ some 22, Merlin is thought to be a tumor suppressor gene involved in cytoskeletal transport and cell architecture. Mutations in this gene have been documented in up to 80% of all meningiomas.13 Additional mutations in other chromosomes such as 1p, 6q, 10q, 14q, 17p, 18q have been associated with an increase in tumor histoplasmic atypia and even malignancy.14,15 Due to their generally benign pathology and slow rate of growth, however, the average time from symptom onset to diagnosis of meningiomas is approximately 4–6 years. As mentioned above, meningiomas most commonly pre­ sent with symptoms related to CN VIII, specifically hearing loss, vertigo, and imbalance. Tumors that extend medially to the petroclival junction can present with pain or facial paresthesia due to involvement of CNV.1,2

Imaging As discussed above, symptomatology, physical examina­ tion, and audiovestibular evaluation cannot diagnose a CPA tumor with a specificity and sensitivity that surpasses MRI. Therefore, MRI is well recognized as both the gold standard and the most efficient examination of suspec­ ted CPA pathology5,16 (Table 24.2). MRI sequences should be performed with and without intravenous gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) and include thin slice (2 mm) pre- and postcontrast T1-weighted sequences in the axial and coronal planes. Comprehensive

Table 24.2: Magnetic resonance imaging (MRI) characteristics of nonvestibular schwannoma cerebellopontine angle tumors

Pathology

T1-weighted

T2-weighted

Gadolinium enhancement

Notes

Meningioma

↓

↑→

Yes

Dural tail

Epidermoid

↓

↑

No

*

Arachnoid cyst

↓

↑

No

*

Lipoma

↑

↑→

Yes

May use fat suppression sequences

FNS

↓

↑

Yes

May be multifocal; enlargement of the FN canal on CT

Hemangioma

↓

↑

Yes

Ca++, bony speculation on CT

Metastasis

↓

↑

Yes

Brain edema, leptomeningeal carcinomatosis

Intra-axial lesions

↓

↑

Yes

Lack of CSF between tumor and brain­ stem; narrowing of CPA cistern

↑, hyperintense; ↓, hypointense; → isointense; FNS, facial nerve schwannoma; CT, computed tomography; CPA, cerebellopontine angle; CSF, cerebrospinal fluid. *Epidermoids and arachnoid cysts may be differentiated on fluid-attenuated inversion recovery sequences (FLAIR) and diffusion weighted imaging (DWI) sequences: only arachnoid cysts will suppress completely on FLAIR and have no restriction on DWI.

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Chapter 24: Meningioma and Other Non-vestibular Schwannoma Tumors of the CPA imaging should also include postcontrast fat saturation as well as heavily T2-weighted three-dimensional sequen­ ces, such as fast imaging using steady-state acquisition or constructive interference in the steady state.16 Diffu­ sion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) can also be performed depending on institutional preferences. Tumor characteristics on MRI, occasionally in combination with computed tomography (CT) and other radiologic modalities, often allow differen­ tiation between various CPA tumor pathologies (Fig. 24.1). On MRI, meningiomas are hypo- to isointense to cere­ bral cortex on T1- and iso- to hyperintense on T2-weighted images. Gd-DPTA transverses the abnormal blood–brain barrier associated with meningioma growth and accumu­ lates in the interstitial tumoral spaces. Therefore, there is avid enhancement with gadolinium in >95% of meningi­ omas. Although heterogeneous intensity on T1-weighted images can be seen in both VS and meningiomas, the T2 signal profile can allow differentiation between these pathologies. Specifically, heterogeneity due to intra­ tumoral cysts demonstrates hyperintensity on T2 images and is suggestive of VS. In contrast, regions of lower inten­ sity caused by calcification will remain low intensity on T2-weighted images and are therefore more consistent with a meningioma. Like VS, meningiomas are typically well-circum­ scribed, sessile masses causing “cortical buckling”, a phen­ omenon in which compression of the adjacent grey matter and distortion of the underlying white matter can be visualized.17 One of the primary features distinguishing it from VS on MRI is the presence of a dural tail, a layer of enhancement extending a few millimeters from the lesion (Fig. 24.2). Histopathologic correlation studies suggest this enhancement could represent either tumor invasion or nontumoral reactive changes, such as hypervascular­ ity, vasodilation, or tissue proliferation or increased per­ meability to contrast. 18 Presence of tumor cells within the peritumoral dura advocates for wide surgical resection of this region to prevent recurrence (discussed in more depth below). Occasionally, a dural tail is observed with an other­ wise appearing VS – this pseudomeningeal sign is not a true dural tail and is related to bone marrow signal in the temporal bone near the porus acusticus. It can be seen on T1 images before and after Gd-DPTA contrast, thereby dis­ tinguishing it from a true dural tail seen only after contrast. Controversy currently exists over meningioma charac­ teristics on DWI or MRS imaging, with some data suggest­ ing lower apparent diffusion coefficient values may be indicative of malignant or atypical histological subtypes.

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Fig. 24.2: Cerebellopontine angle (CPA) meningioma. Axial T1weighted gadolinium-enhanced magnetic resonance image (MRI) demonstrating a left cerebellopontine angle meningioma. Note its broad sessile base and dural tail.

As these parameters have proven unreliable, DWI and MRS imaging are inconsistently used in MRI algorithms.16,17 Unusual imaging features, such as intratumoral cysts, dense calcification, vasogenic white matter edema in adjunct pa­ renchyma and metaplastic changes, are rare, occurring in 20 mitosis per highpower field and features of malignancy are characterized as grade III. They comprise 3% of meningiomas and have a high risk of recurrence and an overall poor prognosis (median 2 year survival of < 2 years after diagnosis).

Treatment As with VS, there are three overarching treatment options for CPA meningiomas, including microsurgical resection, observation with serial imaging, and fractionated and ste­ reotactic radiosurgery. Treatment choice should be guided by tumor pathology, size, location, signs, and symptoms as well as patient age, health, comorbidities, and preference. Selection of surgical approach must be also be indi­ vidualized, and skull base surgical teams should ideally be skilled in multiple techniques. A variety of hearing pres­ ervation [retrosigmoid (RS) and middle fossa] and nonhearing preservation approaches [translabyrinthine (TL) and transcochlear] have been applied to CPA meningi­ omas with success (Fig. 24.5). The RS approach is an efficient and flexible hear­ ing preservation approach commonly employed in CPA meningioma resection. A RS craniotomy allows access to a large portion of the posterior fossa extending from the tentorium cerebelli to the foramen magnum and is ideal

Fig. 24.4: Reticulin staining of a WHO grade I cerebellopontine angle (CPA) meningioma. Reticulin highlights the fibrous collagen deposition common in this histopathologic type of meningioma.

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Chapter 24: Meningioma and Other Non-vestibular Schwannoma Tumors of the CPA

Fig. 24.5: Diagram of various surgical approaches to the cerebellopontine angle.

for meningiomas that extend outside the CPA, but not to the fundus of the IAC. Unlike VS, site of dural origin of CPA meningioma dictates its relationship to the CN VIII nerve bundle and, therefore, influences rates of both hearing preservation and FN injury.21 For example, meningiomas arising anterior to the IAC displace the vestibulocochlear nerve posteriorly and place them at greater risk of injury from an RS approach. Although the RS approach offers the opportunity for hearing preservation, success depends on tumor size and location but may be better than similarly sized schwan­ nomas. Overall, rates of hearing preservation in meningi­ oma resection are greater than that with VS surgery and ap­ proach 100% in some series.22,23 Involvement of the lateral one-third of the IAC, the increased incidence of postoperative headache, and the need for cerebellar retraction are considerations in the RS approach. Extended middle fossa surgery employs a temporal craniotomy to provide wide and direct exposure to the entire IAC and CPA. Bone removal within Kawase’s trian­ gle bordered by the internal carotid artery and the cochlea posteriorly allows access to CPA tumors with IAC and petroclival extension. Limited to tumors with 65 and limited dose to the tumor margin.29 In selected cases, expectant management of CPA meningiomas may be viable treatment option. In general, observation is recommended for tumors that are unre­ sectable due to their location, slow-growing small asymp­ tomatic tumors, as well patients who are poor surgical candidates. In a review of 252 patients with asymptomatic incidentally found meningiomas, one third demonstrated no growth with a mean follow-up of 67 months.30

EPIDERMOIDS Pathogenesis Epidermoids are the third most common CPA lesion, follow­ ing VS and meningiomas. They are congenital rest lesions

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postulated to originate from ectodermal squamous epithe­ lium trapped during neural tube closure between weeks 3 and 5 of intrauterine development.31 Like primary cho­ lesteatoma found within the middle ear and mastoid, the stratified squamous epithelial lining encases desquama­ted keratin and slowly enlarges. Grossly, epidermoid tumors have both a smooth or lobulated surface and a pearly, white capsule consistent with the tumor’s pathogenesis as squamous epithelium. Calcium may be present in 10% of these tumors and epidermoid fluid is typically thick, brown, and viscous resulting from cholesterol and hemo­ siderin by-product of cell membrane decomposition.31 Like many CPA lesions, epidermoids are slow growing with enlargement seemingly parallel to desquamation rates of normal epithelial cells.32 They typically expand toward areas of least resistance, including cisterns, fissures, and ventricles and often occupy multiple intracranial compartments. Although most commonly found intradur­ ally in the CPA or parasellar region, intraparenchymal and fourth ventricle lesions have also been reported.33-35 Unlike other tumors in the CPA, epidermoids tend to surround or encase neurovascular structures instead of compressing or pushing them to the periphery. This feature is of great importance for surgical management as the neurovascular structures often course within the tumor instead of on the external surface. Rarely, epidermoids may degenerate into malignant squamous cell carcinoma.36-38 Due to their slow and insidious growth pattern, epidermoids often reach con­ siderable size before causing symptoms (typically

On MRI, epidermoids demonstrate hypointensity on T1 images and hyperintensity on T2 (Figs. 24.6 and 24.7). However, unlike meningiomas and VS, epidermoids do not enhance with gadolinium. (Minimal enhancement of the epidermoid capsule has been documented in app­ roximately 25% of tumors.31) Epidermoids share similar CT characteristics with arachnoid cysts; both present as well-circumscribed, homogenous, lobulated masses with­ out surrounding edema of adjacent parenchyma. For this reason, CT alone is not sufficient for diagnosis.39 On MRI and CT, epidermoid and arachnoid cyst contents match the density and intensity of CSF. However, specific MRI sequences allow distinction between these two patho­ logies: epidermoids are differentiated from arachnoid cysts by their relative hyperintensity to CSF on FLAIR (fluid-attenuated inversion recovery sequences) and DWI sequences. Other lesions with FLAIR and DWI hyperin­ tensity include abscesses and cholesteatoma. These can be differentiated from epidermoids by thick rim enhance­ ment and temporal bone destruction, respectively.31

Fig. 24.6: Cerebellopontine angle (CPA) epidermoid. Axial T1weighted magnetic resonance imaging (MRI) of a CPA epidermoid demonstrating low signal intensity. Note the compression of brainstem and fourth ventricle.

Fig. 24.7: Cerebellopontine angle (CPA) epidermoid. Axial T2weighted magnetic resonance imaging (MRI) of a CPA epidermoid demonstrating hyperintensity. Note cranial nerves VII and VIII visible in the internal auditory canal.

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hear­ing and balance related complaints). Although large at presentation, epidermoids rarely present with obstruc­ tive hydrocephalus as the fissured, cystic wall allows CSF spread around the tumor. Patients with epidermoids may occasionally present with chemical or aseptic menin­ gitis from extrusion of cyst fluid into the subarachnoid space.34

Imaging

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Chapter 24: Meningioma and Other Non-vestibular Schwannoma Tumors of the CPA Areas of contrast enhancement within epidermoids have been reported in the literature and have been shown to correlate with malignant transformation to squamous cell carcinoma, an extremely rare event.36-38,40,41 Also rare are “white epidermoids”—tumors whose high protein­ aceous content leads to reverse signal intensity with hyperintensity on T1 and hypointensity on T2.31,42

Treatment Treatment of epidermoids is gross total resection, often via an RS craniotomy.31 As discussed previously, these tumors are typically avascular and friable, but may encase or even adhere to neurovascular structures within the CPA. To avoid permanent nerve or vascular injury, subtotal resec­ tion with preservation of vital structures has been strongly advocated. Although subtotal resection would intuitively suggest a higher risk of recurrence, there are studies sup­ porting similar recurrence rates following total and sub-/ near-total resections. 43 Overall, published data suggest a high rate of hearing preservation for subtotal resection, even if performed for the second time.44,45 At present, data on GKS of epidermoid tumors are scarce. For tumors with malignant transformation, the addition of adjuvant radio­ therapy to surgical resection appears to confer a survival benefit.46

FACIAL NERVE SCHWANNOMAS Pathogenesis Schwannomas of the FN can occur anywhere along the FN course and intratemporal lesions are often multifocal. Although most commonly located in the perigeniculate region, facial nerve schwannomas (FNS) may also occur in the CPA.10,47 Isolated CPA FNS represent 45°) • Distance > 20 feet • Visual barriers Speaker variables

• • • • • • • • • • • • •

Lab, lamb

lipreading-only stimulation, and other modalities as well (auditory-only, or combined auditory-visual stimulation). Speechtracking is a vehicle for teaching the patient and communication partner repair strategies (see below and Table 31.5) to cope with a situation when there is a failure to lipread accurately. After experiencing several sessions of speechtracking, the speechreader becomes more efficient and increases the number of words per minute that can be tracked.

MAXIMIZING THE AUDITORY CHANNEL: AUDITORY TRAINING The act of applying a sensory aid (be it a hearing aid, osseo integrated device, cochlear implant or something as yet to be conceived) does not imply that the person using it will be able to obtain full benefit from the signal provided for a variety of reasons. Though we often talk about limitations in the neural survival that may impose restrictions on signal encoding, auditory training may allow improvement in performance with a device despite distortions imposed by the auditory system. There is strong evidence that auditory training is effective in changing behavior (see Sweetow & Palmer24 for a comprehensive review of the literature.) The levels of function that are targeted in an auditory training program are outlined and defined in Table 31.3. As seen in this hierarchy, a person with a hearing loss may initially have poor sound awareness on a reliable basis despite the signals being presented at a loud enough (i.e. suprathreshold) level. With training, however, the reliability of that awareness will increase and it is possible to proceed through the hierarchy to be able to discriminate stimuli, such as two-syllable versus three-syllable words reliably. Once that level of skill is mastered, recognizing words in isolation or in sentences would be the next goal. Finally, comprehending connected discourse would be the long-term objective.



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contextual cues, it is possible to understand the sentence “Fry the egg in the pan” without confusing the word “pan” with its homophenes (from Table 31.2) “man” and “ban”. For the child acquiring language through an impaired auditory system, and using vision as a modality to supplement diminished input through sensory device(s), the task is entirely different because he or she is in the process of learning a lexicon and the rules of syntax simultaneously while learning the process of lipreading. Training methods involve encouraging the speech reader to follow the gist of the conversation, rather than relying on a word-for-word understanding. This is referred to as a synthetic approach. At the same time, this dyna mic method is supplemented by drills that increase the patient’s speed and accuracy of comprehension, both for single words and for sentences, which is a more analytic approach. A practice technique that has gained wide use is speechtracking23 in which the speechreader shadows the clinician and must repeat read materials accurately; records are kept of the number of words per minute that the patient is able to repeat in a trial, which may consist of



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Facial hair (beards or moustaches) Chewing gum Smoking Extraneous gestures or putting hands near/in front of mouth Holding hand(s) in front of mouth Exaggerated articulation Insufficient mouth movement Foreign accent Rapid speech Thin lips Facing or turning away from communi­ cation partner Speaking from the side of the mouth Gender of the speaker (females better perceived) Complex sentence structure

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Table 31.3: Levels of auditory function and auditory training progression

Easy

Awareness

Can tell that a sound is present; cannot necessarily describe its characteristics

↓

Discrimination

Can tell that two sounds are diff­erent from each other; may not be able to recognize or repeat either sound

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Identification

Can tell what the sound is

Difficult

Comprehension Can understand the sound and its implications

Many persons with hearing loss begin at a level that is apparently initially higher than described in the scenario above. Such individuals may have satisfactory function in quiet, but experience significantly reduced performance in adverse listening situations (as well as perceiving signi­ ficant activity restrictions and participation limitations or handicap). As indicated in Table 31.4, well-recognized factors that degrade the auditory signal are background noise, reverberation (echo), and competing speech, among others. An auditory training program teaches the patient (1) to manipulate the environment to reduce these adverse conditions whenever possible and (2) through practice, to perform better under such challenges as progressively increasing signal-to-noise ratios. Individualized, one-on-one therapy may be supplemented by the use of materials that have been generated to permit the person with hearing loss to develop or practice skills independently. Programs for practicing lipreading or auditory skills are widely available for use with home computers. Among these programs, Seeing and Hearing Speech25 Read My Quips26 and Conversation Made Easy27 provide training in both auditory and visual domains. One of the most widely used and validated programs is the Listening and Communication Enhancement (LACE).28 As initi­ally described by Sweetow and Henderson Sabes,29 this program has the goal of “…better comprehension of degraded speech, enhancement of cognitive skills, and improvement of communication strategies” (p. 243). The recommended practice regimen is 30 minutes per day for 5 days per week for 4 weeks (10 hours total). During the LACE program, the patient listens to three types of degraded signals: time compressed speech, as a practice for rapid conversation; speech with a multitalker babble background; and speech with a single competing speaker background. The program also contains routines for increa­sing auditory memory and processing speed, as well as developing improved communication strategies.

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Table 31.4: Factors that adversely affect auditory signal transmission

Factors Environmental • Background noise variables • Competing speech • Reverberation (echo) • Distance (affects intensity of direct signal and, thereby, signal-to-noise ratio) • Physical barriers • Sun or fluorescent light source (may affect performance of assistive listening device) Speaker variables

• Fundamental frequency of voice • Spectrum of speech (females or children may be poorly perceived in high-frequency hearing loss) • Habitual loudness of voice • Rapid speech • Complex sentence structure • Foreign accent • Inadequate/substandard articulation

Use of music in auditory training has been discussed by several authors.30-32 Music may be a means of teaching rhythm or intonation to children with hearing loss.30 Musical timbre is poorly represented in current cochlear implants33-36 while temporal envelope cues are more accessible.37 Gfeller et al.33 showed that timbre recognition was amenable to training, leading to the possibility that patients motivated to improve aspects of their musical perception may be able to do so with intervention. Musical enjoyment is also of great importance to adult cochlear implant users in enhancing quality of life.38,39 Less systematic research has explored the satisfaction of hearing aid users in regard to music.

COMMUNICATION TRAINING Given a successful fitting with a hearing aid or other sensory device and active engagement with counseling about methods to improve communication, one of the dimensions that will be addressed is how to deal with occurrences of communication failure. Given the limited visibility of speech sounds, the environmental and speaker variables that may limit the visibility (see Table 31.2) or the acoustic transmission (Table 31.4) of the communication signals, it is understandable that instances of inadequate reception or misunderstanding may occur multiple times during any conversation. It is necessary for the person with a hearing loss and his/her communication partner to learn methods to “work through” such misunderstandings.

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Chapter 31: Aural Rehabilitation and Hearing Aids

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sentence requires the person with hearing loss to be willing to engage with both familiar and unknown persons about what modifications in conversational behavior will make it easier to communicate. Therefore, one aspect of communication therapy is reinforcing the use of appropriate assertiveness, a difficult change in behavior that requires practice in many venues, and which the audio logist will guide in development. In most instances, patients with hearing loss who are seen for therapeutic communication training typically use some form of amplification.

AMPLIFICATION IN REHABILITATION

Table 31.5: Repair strategies

Repeat the sentence

In many cases, amplification is an integral step in the treatment of hearing loss. More so than at any other time in history, there is a greater variety of amplification options available. This includes not only a tremendous array of hearing aid styles, circuit types, and processing schemes from a wide variety of manufacturers but also a proliferation of assistive listening devices (ALDs) that function either independently of, or in conjunction with hearing aids, often employing either FM or Bluetooth techno logy. Hearing aid technology is continually changing, and the last 10 years have been no exception. From smaller physical size to better, more sophisticated processing algorithms, the ultimate goal is always to provide greater benefit for the hearing aid user.42 ­







Table 31.5 summarizes a series of techniques that may be used to repair communication breakdowns.40 These strategies are used in a communication partnership in which a cooperative speaker is modifying his/her message, not in its content, but in its method of presentation, when the partner with hearing loss indicates misunderstanding or responds inappropriately in conversation. Thus, when there has been a communication failure, the speaker has options other than only repeating verbatim what was just said. She might, e.g. simplify the sentence or rephrase it, or give a key word in order to get meaning to be clarified. Another component of communication training is teaching Clear Speech41 to communication partners, as well as training the person with hearing loss how to instruct others in what actions enhance the clarity of speech. As listed in Table 31.6, Clear Speech is a sensible approach to communication with a person with hearing loss. It entails slow presentation rate, normal articulation, and phrasing in reasonable length sentences. Suggesting to a communication partner, sometimes a stranger, that he/she modifies speaking style as an accommodation for your hearing loss demands assertiveness. Requesting such accommodations is not natural to most people. Asking a speaker to face you or rephrase a difficult

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Hearing Aids

Simplify Rephrase

Generally speaking, hearing aid styles are named on the basis of how they are worn and their physical size. The choice of hearing aid style should be made based on factors such as gain/power requirements, physical features of the ear canal (size, contour, etc.), ease of insertion and manipulation, need for specific features (directional

Give a keyword Select a more visible alternative word Provide a definition of the difficult word Break information up into two sentences Source: Based on Tye-Murray.40

Table 31.6: Elements of clear speech

Element

Error made in uncontrolled conversation

Clear speech approach

Rate

Rapid

Slowed (not labored) presentation

Phrasing

May ignore sentence breaks or continue with run-on sentences

Pauses interjected at ends of phrases or sentences

Articulation

Slurred or exaggerated

Natural articulation with an aim at clear pronunciation

Loudness

Too soft, or when attempting to compensate for a person with hearing loss, too loud

Natural presentation at a moderately loud level but not shouted

Emphasis on key points in sentences

Emphasis may be haphazard

Emphasis on key words

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microphones, telecoil, etc.), physical comfort and occlusion considerations, and cosmetic concerns.43 Currently, the most common styles of hearing aids are behind–the– ear (BTE), in–the–ear (ITE), and over–the–ear (OTE) types. Although eyeglass and body aid style devices are still available, they account for a minor percentage (10 dB at 2000, 4000,

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Figs. 32.2A and B: Vibrant Soundbridge. (A) Vibrating ossicular prosthesis (VORP) schematic with close-up view of floating mass transducer (FMT). (B) Approximate location of VORP and standard S-shaped incision. (C) VORP in situ. (D) Placement of FMT in incus vibroplasty.

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The application of direct vibratory stimulation to middle ear structures (i.e. by way of a middle ear implant) has been termed vibroplasty. Although incus vibroplasty was the intended purpose of the VSB device (Fig. 32.2D), seve ral variations have proved successful. In round window vibroplasty, the FMT is placed against the round window membrane and stimulates it directly. In a retrospective study of 50 patients from 2013, Colletti et al. have demons trated the safety and efficacy of this technique in patients with moderate to severe mixed hearing loss resulting from a variety of ossicular chain and other middle ear pathologies.9 A third variation on the vibroplasty involves the use of surgical devices termed couplers. Coupler vibroplasty involves the interposition of a metallic device optimally shaped to fit the round window, oval window, or head of the stapes.10 Given the magnetic nature of the FMT, concerns regar ding the safety of magnetic resonance imaging (MRI) have been raised. A retrospective questionnaire study by Todt et al. has found noise, middle ear pain, and pressure at the receiver bed to be frequent complaints among VSB implantees undergoing MRI. In two (of thirteen) cases, alterations in FMT position required surgical reposition ing via a transtympanic approach. None of the patients experienced SNHL after MRI scanning.11 Wagner et al. in a review of the literature, found no evidence of injury to middle or inner ear structures as a result of MRI scanning. Furthermore, no cases of FMT demagnetization have been reported. In their review, the authors argue that 1.5 Tesla MRI can be carried out at calculated risk, provided that a clear and compelling indication exists.12

Middle Ear Transducer (MET) and MET Carina (Otologics, LLC, Boulder, CO, USA) The MET, also known as the MET Ossicular Stimulator, was a semi-implantable middle ear device manufactured by Otologics, LLC (Boulder, CO, USA).13 Eventually, it came to be replaced by a fully implantable version, the MET Carina (Fig. 32.4A).14 The two devices share a common actuator but differ in that the MET Carina’s microphone and rechargeable battery are placed beneath the skin. The origin of the MET dates back to the 1970s, when Dr. John M. Fredrickson induced vibrations of a magnet implanted onto the stapes of rhesus monkeys using an electromagnetic coil. By the 1990s, Drs. Fredrickson, Coticchia, and Khoslaat (Washington University, St Louis) had demonstrated that safe stimulation could be accomp lished using an electromechanical, motorized transducer ­

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and 6000 Hz) relative to presurgery-aided hearing for all 53 subjects. Feedback and occlusion were essentially eliminated. Further statistically significant improvements were noted in terms of patient satisfaction and device preference.6 A 2008 study by Mosnier et al. aimed to provide long-term follow-up data by examining the first 125 patients in France at 5 to 8 years postimplantation (compared with initial follow-up). This study found no change in functional gain for the frequency range of 500 to 4000 Hz and a high satisfaction rate of 77%. Seven patients in this study required reimplantation for device failure; however, failures were only observed in patients implanted before 1999, the year in which the device underwent redesign.7 In a review of 1000 cases by the manufacturer published in 2005, device failure rates were reported to be 0.3%.8



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Fig. 32.3: Vibrant Soundbridge: Manufacturer’s clinical and audio metric criteria for implantation. (CHL, conductive hearing loss; FMT, floating mass transducer. MHL, mixed hearing loss; SNHL, sensorineural hearing loss).

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A

B

Figs. 32.4A and B: (A) Otologics MET Carina fully-implantable system. (B) Diagram of MET Carina in situ. (MET, middle ear transducer).

placed into a laser-drilled sleeve in the incus of rhesus monkeys. In 1996, the MET technology was sold to Otologics, LLC, which relocated to Boulder, CO, USA. The Food and Drug Administration (FDA) evaluation began in 1998 and by 2000 a semi-implantable version of the device was available in Europe. In 2006 the Otologics fully implantable MET received the European CE-mark. For both devices, the implantation procedure begins by exposing the mastoid cortex through a postauricular incision. The middle ear is approached through a limited mastoidectomy, essentially a modified posterior attico­ tomy fashioned by tunneling between the external auditory canal and the tegmen mastoideum until exposure of the incus body and malleus head is achieved (Fig. 32.4B). A metallic stage is affixed to the ledge of cortical bone surrounding the cavity. A KTP laser incudotomy is then performed, targeting the posterosuperior aspect of the incus; then, the transducer probe is embedded into the orifice. In the case of the MET Carina, the receiver and trans­ducer are positioned into a well drilled on the retromastoid cortical bone, and the microphone may be placed at the mastoid tip or in the retroauricular region.14 At least one case of successful round window implanta­ tion via a facial recess approach has been reported.15 Figure 32.5 summarizes the audiometric selection criteria for implantation.

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Fig. 32.5: MET/MET carina. Manufacturer’s audiometric criteria for implantation.

Bruschini et al. studied outcomes of MET Carina implan­ tation in eight adult patients with moderate to severe sen­ sorineural and one with mixed hearing loss. All patients showed improvements in speech perception abilities and reported subjective benefits. The main adverse effect identified consisted of feedback noise in seven patients. This problem resolved with minor fitting adjustments in

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Chapter 32: Implantable Middle Ear and Bone Conduction Devices

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Esteem Hearing Implant (Envoy Medical Corporation, St. Paul, MN, USA)



Envoy Medical Corporation (St. Paul, MN, USA) was originally founded as St. Croix Medical in 1995, with the mission to develop and market the first fully implantable hearing aid that did not require a microphone or speaker. In 2004, clinical trials began in the United States and in Europe, with subsequent European CE Mark approval in 2006. In 2010, the FDA approved the Esteem Hearing Implant for commercial distribution.22

The Esteem Hearing Implant is a fully implantable device with a piezoelectric actuator. In contrast to other implantable hearing devices, the Esteem uses the tympanic membrane and malleus as a microphone. A piezoelectric sensor surgically fixed to the incus detects vibrations of the tympanic membrane. It then routes these signals to the processor, which amplifies them before delivering them to the piezoelectric actuator, which vibrates the stapes directly (Figs. 32.6A and B). To avoid feedback, implantation requires the disarticulation of the ossicular chain at the incudostapedial joint, along with resection of a 2-mm segment of the long process of the incus. The approach is performed through wide-field canal wall up mastoid ectomy with extended facial recess dissection. The device is powered by a nonrechargeable battery, which may last 4.5 to 9 years, depending on usage. A significant disadvantage is that replacement of the battery requires surgical inter vention. Figure 32.7 summarizes the manufacturer’s clinical and audiometric selection criteria for Esteem implanta tion. Disarticulation of the ossicular chain is another signi ficant drawback, since it introduces a maximal conductive hearing loss. Following implantation, a patient is obligated to keep the device turned on to hear, in contrast to other devices, which preserve the ossicular chain and therefore maintain patients’ baseline, albeit impaired, hearing. In a prospective, nonrandomized, multicenter FDA phase 2 trial, 57 subjects with bilateral, mild to severe SNHL were implanted. Improvements were noted in terms of speech reception threshold (29.4 dB compared with 41.2 under best-fit aided conditions, p  360mg, or hearing loss. On average, they used 1.5+/– 0.51 injections. The Postema132 study used a dose of 30 mg/mL of gentamicin once a week for 4 weeks. In both groups, vertigo control was superior in the gentamicin group than the control group. In the Stokroos study, vertigo spells fell from a very high 74 events/6 months to 0 events/6months in the gentamicin group, and from 25 to 11 events/6 months in the placebo group. Clearly the starting point of severity was very different in the active and placebo arms, but despite the higher severity, apparently the gentamicin group did much better. In the Postema study, a visual analogue vertigo score was used, and scores fell 2.1 to 0.5 in the gentamicin group, with no change (2.0 to 1.8) in the placebo group. Confusingly, despite the 100% control for the gentamicin arm in the Stokroos study, the same group seems to have published a retrospective review of their vertigo control, presumably including some of the same data set, of only 61.4% in 2007.134 In the Stokroos study, neither active or control groups showed significant hearing loss. The Postema study reported a fairly high incidence of hearing loss, the ave rage hearing loss was 8.1dB in the gentamicin group, with 4 patients (25%) showing a hearing loss greater than 25 dB. ­

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as 1948, Fowler124 described the use of systemic streptomycin to treat Meniere’s disease. Shuknecht125 first described IT injection of streptomycin in 1957 to treat Meniere’s disease, with a high rate of hearing loss. Later, lower dose IT gentamicin strategies were adopted that allowed preservation of hearing with resolution of symptoms.126 Different treatment philosophies for Meniere’s disease have been espoused, from a goal of total ablation of the vestibular labyrinth using a fixed maximal dose protocol, to minimal therapy to control symptoms without necessarily ablating the labyrinth, i.e. titrating to effect. There have been several systematic reviews on the use of gentamicin for Meniere’s disease.127-131 For instance, Chia et al.129 reviewed 27 studies, most retrospective, and found an overall vertigo control score of 73.6%. They found lower dose studies tended to have lower vertigo control scores. In the same study, they found overall hearing loss rates of about 25.1%, and in this review they also included multiple daily dosing regimens, which had a hearing loss rate of 34.7% versus about 24% for other types of delivery. In general, the proportion of profound hearing loss subjects was also higher in the multiple daily dosing studies. They report that patients that achieved complete vestibular ablation, tended to have a higher rate of complete vertigo control (92%) than those with partial ablation (75%). Cohen-Karem et al.128 in the same year (2004), reviewed 15 studies, of which about half were retrospective studies and half prospective studies. The AAOHNS Committee has published a scoring system for control of Meniere’s disease vertigo, ranging from A to F, which is based on dividing the number of attacks of vertigo from 18 to 24 months post treatment by the number in the 6 months prior to treat ment. Class A (total control) or B (substantial control) is usually considered successful treatment. Cohen-Karem et al. found an overall vertigo control rate of 74.7% for class A control, and 92.7% for class A or B control in gentamicin studies. The overall reduction in hearing was 1.5 dB, which was not statistically significant from zero in their analysis. The most recent systematic review, by Huon et al. in 2012,131 included over 559 patients in 14 studies that were all prospective, of which two were placebo controlled and double blinded. These studies covered a variety of protocols, but none of the ones reviewed were the very high-dose multiple daily injections protocols. The mean dose was 2.1 injections. These authors found that control of vertigo in the total population was class A in 71.4%, Class B in 16.1%, Class C in 4.3%, Class D in 2.4%, Class E in 2.9% and Class F in 2.9%. Overall successful treatment (Class A and B) was found in 87.5% of patients. The mean weighted PTA and

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None of the studies really comment on overall health of the patients. For instance, Boleas-Aguirre et al.135 note that 15.5% of patients experienced dizziness after gentamicin injections, which may not be captured with vertigo reporting alone. Also, if there is vestibular damage, there maybe long-term consequences as this patient population ages, with aging related vestibular, vision and proprioceptive losses. It is not clear, however, that gentamicin in low-dose protocols causes significant vestibular damage, caloric results from these studies are difficult to assess, but do not always show evidence of vestibular loss, and it may be possible that gentamicin in low doses may control vertigo without a necessarily a vestibular ablative effect. For instance in the Stokroos study,133 there was no change in the cumulative caloric response in either the active or the control group.

Otoprotection Acquired hearing loss occurs in various insults that can interact with each other. The most commonly identified ototoxic insults are noise, aging, and drugs, most often cisplatin and aminoglycosides. There are many compounds that have been shown to be otoprotective, if given around the time of a major insult, but primarily these have only been proven in animal studies. Almost all agents work much better if given in a pre-exposure phase, as opposed to a postexposure phase; it remains a challenge to find agents that are effective when administered significantly delayed after exposure. If the damage is primarily to hair cells, then the fact that SGN death is much delayed after hair cell loss3 allows a window of opportunity for salvaging SGNs after hair cell damage has already occurred. A common mechanism for damage in many tissues is through the side effects of aerobic respiration, which generates ROS. Many ototoxic insults cause damage by increasing the generation of ROS through oxidative stress in all compartments and cell types in the cochlea, which are a strong activator for apoptosis pathways. The apop­ totic cascade itself can also generate ROS, rather than being the initiator of these pathways. For instance, Shulz et al.15 found that blocking caspases, in addition to mitigating apoptosis, also blocked ROS formation, and similar findings have been reported for BDNF (a NT) inhibition of apoptosis.136 Most drug strategies are either antioxidant in nature and act to block ROS, or are anti-inflammatory, which encompasses many effects, some of which are also antiapoptotic. Experimental drugs are available to specifically block elements of the apoptotic pathway.

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The literature in the field of otoprotective agents is rather muddied, with many conflicting studies, with a large number of agents found to be effective in animal studies. Few or these translate to human studies, and often these are not of sufficient quality or power to show efficacy. For noise-induced damage studies, a precaution is that the mechanisms for temporary threshold shift (such as mechanical buckling of the stereocilia) are different from those of permanent threshold shift, and drugs effective against one may not be effective against the other. Despite this, many human studies focus on the effects of drugs on temporary threshold shifts. Some compounds found effective in vitro cannot cross the RWM, but may be induced to do so in the future with novel drug delivery agents, and this field is rapidly evolving. Otoprotective drugs tested in human clinical trials (for review see ref.137) can be categorized into:

Antioxidants This is probably the largest category of otoprotective drugs. Here we can only briefly touch on a few examples. The most important cellular antioxidant is reduced glutathione (GSH). Some drugs such as N-acetylcysteine (NAC) and d-methionine are prodrugs for replenishing glutathione, others are exogenous antioxidants. A clinically used antioxidant is sodium thiosulfate for cisplatin toxicity. This thiol containing compound unfortunately also binds cisplatin, and inactivates it.138 This is its major limitation, as it decreases the antitumor efficacy of the cisplatin. This is a large molecule compound, and does not seem to be effective administered IT.139 D-methionine, which raises antioxidant levels, has also been studied extensively in cisplatin induced toxicity140,141 and found to reduce toxicity, and also has been studied in noise induced hearing loss.142 However, it also binds cisplatin and may reduce its efficacy. NAC has been shown to protect against many types of inner ear damage in animal studies, and particularly studied is its effect against noise.143,144 It has been shown to be effective in industrial noise settings in humans145 in some trials, but not in others,146 and trials are ongoing testing its otoprotective effects against cisplatin.137 For a review of NAC mechanisms of action and animal data, see Kopke et al.147 A recent trial of IT 2% NAC for cisplatin ototoxi­ city did not find significant hearing preservation benefit overall in the whole group (using the contralateral ear as a control,148 but did show a significant effect in two of the tested patients. A similar study using IT 10% NAC found a

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Chapter 35: Inner Ear Molecular Therapies







challenged explant hair cells, steroids have been found to be very effective in reducing apoptotic cell death.169 Glucocorticoid receptors are found in hair cells, spiral ligament, and SGNs, and seems to work via both the classic described action of genomic nuclear binding via the GR receptor and controlling transcription of genes, as well as via a much more rapid nongenomic pathway that regulates immune responses (for review, see ref.170). Indeed, the mechanisms of action of steroids are complex and multifold. At a systemic level, they reduce circulating white cells and inflammatory mediators and prevent release of many proinflammatory agents such as cytokines, TNF-α, interferon, interleukins and many others.171 These will reduce systemic inflammatory responses, including those that might affect the inner ear. Some authors have proposed172 that the majority of effects of autoimmune inner ear disease are not due to inflammation in the inner ear, but rather on the vasculitis that results from systemic inflammation, which results in loss of the endolymphatic potential by damaging the ion-flow limiting action of normal epithelial tight junctions, leading to inner ear cell damage. There is some data supporting this, as inner ears of subject temporal bones with immune mediated inner ear disease rarely show evidence of direct inflammation.173-175 Glucocorticoids can help restore the BLB172 by limiting this vasculitis. To support this hypothesis, a inflammatory response created with lipopolysaccharide (which results in a vasculitis and tissue damage) can be mitigated with dexamethasone.176 In addition, steroids may change ion gradients in the inner ear by affecting Na-K-ATPase and potassium secre tion by marginal cells, as well as up regulating genes associated with other ion channels and aquaporins.177,178 Indeed, combination therapy with mineralocorticoids and glucocorticoids may be efficacious when either alone is not, as shown in an animal model of autoimmune inner ear disease.179 In the inner ear, while glucocorticoids may bind to the high affinity mineralocorticoid receptor, blocking binding to the GR receptor causes increased susceptibility to noise damage in mice, dexamethasone administration reduces it, and blocking binding to the mineralocorticoid receptor has little effect,180 suggesting that the mineralocorticoid effect is not important in protection from acoustic trauma. Modulation of steroids in the hypothalamic pituitary axis is also thought to be the mechanism for sound conditioning, in which prior exposure to low levels of sound protect animals against later acoustic trauma.170







mild benefit at 8 kHz, but this mild effect at this frequency is clinically not meaningful.149 NAC has been used in military settings. Other antioxidants studied include Gingko Biloba, found to be effective against cisplatin ototoxicity in rat studies,150 and Alpha Lipoic Acid, which also shows efficacy against a variety of insults in rat.151-153 A human trial testing protection against cisplatinum is ongoing.137 Ringers lactate has shown protective activity in some studies,154 but not in others.155 Some vitamins and dietary supplements are also powerful antioxidants. Animal studies suggest that antioxidant vitamins such as A, C, and E can act to reduce noise induced hearing loss,156 sometimes in combination with magnesium. Resveratrol (found in red grapes) has also been shown to protect against hearing loss in rats.151 Other supplements variably found to be protective in animal studies include melatonin,157 acetyl-L-carnitine, and lazaroid.142,157 Other potent antioxidants studied have been ebselen, in combination with allopurinol, and found in animal studies to reduce cisplatinumdamage158 and noise induced damage.159 Lecithin has also been reported to be active in otoprotection.160 Also very intriguing are the various classes of flavonoids that seem to have numerous neuroprotective effects, a large portion of which are through preventing ROS formation.48 Despite these advances, what is missing is a potent oral antioxidant that has been well studied in humans, and shown to be effective against a wide variety of insults.

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In animal studies, salicylates have been found to be otoprotective in cisplatin toxicity,161 in noise-induced hearing loss,162 and in humans in a Chinese study on gentamicininduced hearing loss.163 Steroids are used extensively in otology, and will be reviewed in more detail here. The inner ear contains receptors for both glucocorticoids, and mineralocorticoids, the affinity of the mineralocorticoid receptor is much higher than the glucocorticoid receptor, and the mineralocorticoid receptor is probably fully saturated at basal body levels, whereas the glucocorticoid receptor is not.164 Several studies in animals and cochlear implants have shown mitigation of hearing loss,165-167 both in terms of cell preservation and in terms of hearing recovery post cochlear implantation (for review see ref.168). In various models, including tumor necrosis factor alpha (TNF-α)

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ANTI-INFLAMMATORY DRUGS

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As seen above, how exactly glucocorticoids protect the cochlea is not well understood, their effects on the inner ear are extremely complex. In an Affymetrix gene array study, steroids were found to alter the expression of over 8000 of the 17,500 genes identified in the mouse ear within 6 hours.181 Many of these are genes controlling inner ear hemostasis and the BLB, which may be a more important function than any direct anti-inflammatory effect. TNF-α inhibitors have also been used in inner ear otoprotection. Many forms of damage lead to proinflammatory cytokine release, and TNF-α antibodies such as infliximab or etanercept can provide protection from cisplatinum ototoxicity in66,182 animals, and in autoimmune hearing loss.67,183 Apoptosis inhibitors would be very useful in many cell death pathways. Inhibitors of the JNK cascade by drugs such as AM-111 and SPB00125 by IT injection have been found to show effective otoprotection in animals.70-72,184-186 AM-111 has been used IT in a small group of human subjects and found protective against noise-induced hearing loss, but this study was without a control group.187 In other experimental approaches, inhibitors of caspase 3 and 9 protected against cisplatin ototoxicity188 in guinea pigs. Rolipram is another promising agent that prevents apoptosis by downstream upregulation of cAMP and BDNF and TRKB targets.189

NEUROTROPHINS (NTS) Because there is continuous NT support of the SGNs by hair cell secretion of NT-3 and BDNF, hair cell loss can lead to subsequent SGN loss. This has been noted in numerous studies (see ref.190 for review). Sometimes loss of SGNs can occur alone, without hair cell loss, e.g. through excito­ to­xicity by prolonged stimulation. In a later section, we will review the role of NTs in hair cell differentiation and as growth factors, but here we will review their otoprotective role. Neurotrophic support seems crucial to prevent apop­ totic cell death. This has been demonstrated for various cell types in various studies.191 NTs seem to provide tonic suppression of proteins in the apoptotic cascade.192 Withdrawal of NT support seems to increase intracellular ROS in cultured auditory neurons,193 and interestingly, blocking caspases not only blocked apoptosis, but also ROS formation.15 NTs have a host of effects in neuronal and hair cells, including calcium homeostasis,194 and regulation of endo­ genous free radical scavengers.15,136,193

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NTs have been shown to protect inner ear cells from a variety of insults, e.g. noise, ototoxicity,195 and aminoglycoside toxicity.196 Why hair cells, NT secretors, are also protected is not clear. It maybe that hair cells also require trophic support from SGNS, and there may be complex local NT recycling networks. In humans there is a window of opportunity between hair cell loss and SGN loss in which NTs may have utility as therapeutics. This has been studied extensively for NT-3 and BDNF, and to a lesser extent with GGNF, and much less so with nerve growth factor (NGF).190 Unfortunately, this protective effect requires an ongoing supply of NTs, so requires some ongoing source of NT delivery or production.197 Other studies have not shown such a dramatic loss of protection after NTs were stopped,198-200 and it has been speculated that this is because electrically stimulated eABRs were used to measure hearing function, which could have acted as SGN protectant. A few authors190,201 have shown that continued electrical stimulation could preserve SGNs after exogenous NTs were stopped. Another possibility is that SGNs take on an autocrine mechanism and can start to secrete their own NTs. It is at present unclear if electrical stimulation is adequate in humans to preserve SGNs if they were prevented from dying by temporary NT support initiated soon after hair cell loss. This would be a useful strategy in cochlear implantation if proven to be effective. Almost all types of NTs, whether expressed in the adult cochlea or not, seem to have a protective effect on SGNs. It seems, however, that the morphology and functional aspects of response may vary by NT.202,203 NTs have been delivered through a variety of approaches. The most effec­ tive route is intracochlear injection (including through cochlear implants), other somewhat less effective methods are IT injections, and IT infusion with hydrogels, Gelfoam (Upjohn, Kalamzoo, MI), and alginate beads.204-206 In addition to SGN survival, NTs can also increase axonal sprouting of peripheral processes of SGNs toward the hair cells.207 This could be used to bring peripheral processes closer to cochlear implant electrodes for instance.

INNER EAR DRUG DELIVERY METHODS Inner ear drug delivery mechanisms have been devised to provide drugs over a longer period of time, to control drug release, or to increase drug concentration inside the inner ear.

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The commonest method to deliver drugs directly to the inner ear, apart from systemic administration, is via direct IT injections. These are simple and cost effective, even with multiple injections, and well proven. IT injections provide a “bolus” of drug, but have little or no sustained delivery of the drug. IT injections are plagued by various limitations. Firstly, the solutions are usually low viscosity, and easily run down the Eustachian tube. The dose delivered is unpredictable, and may vary from patient to patient, or from injection to injection. More viscous or gel formulations may stay in the middle ear for longer, and provide a more controlled and repeatable dosing scheme. Secondly, bolus administration results in high peak concentrations over a short time, but low plateau concentrations. These high peaks may be harmful so some inner ear tissue that it would be advantageous to preserve. Sustained release formulations may result in better-targeted or more potent effects on the target tissue. Thirdly, the primary entry point to the inner ear is the RWM, which has varying degrees of permeability to various compounds. Carriers maybe able transport the drug across the RW, or the RW can be made more permeable to the drug. Despite these limitations, as of yet, there is little convincing evidence in humans that any other drug delivery mechanism outperforms direct IT injection for common drugs such as steroids or gentamicin. However, there are many drugs that will likely not achieve adequate concentrations inside the inner ear by IT injection alone, and this limits the scope of IT therapy to only a few drugs currently.



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Intratympanic Injections



Otologic surgeons have long experience in opening the inner ear and preserving hearing through operations such as stapedotomy or lateral canal fenestration. More recently, the cochlea itself has been opened for cochlear implantation in hearing preservation short electrode implants, and it is now accepted that hearing preservation is possible despite insertion of an implant into the ST. Direct injection is likely to result in the greatest concentration of drug in the inner ear. However, cochlear opening (e.g. for cochlear implantation) is rarely, if ever, performed in the presence of good residual hearing in the high frequencies that reside at the basal region near the RWM. If intracochlear therapies are used to address ears that are still hearing well, there is understandably concern as to the hearing risks. This has led to development of new techno logies and drug injection techniques that are less trauma tic to the inner ear. Methods to access the inner ear directly include stape dotomy, round window injection, endolymphatic sac (ELS) injection, lateral canal fenestration and cochleostomy. Gadolinium injected into the human ELS was shown to reach all areas of the cochlea without residual hearing damage,208 and in animal studies, ELS dexamethasone injec tions were able to modulate aquaporin 3 expression.209 Access to some compartments maybe preferentially achieved by injecting in specific areas, e.g. injection via stapedotomy will allow better access of vestibular compartments than round window injection. To minimize the hearing loss risk inherent in opening the cochlea, some researchers have tested accessing cochlear fluids by opening the vestibule instead, e.g. Praetorius et al. were able to show expression of viral particles introduced into the vestibular system in both the vestibular and cochlear organs.210 The semicircular canals have also been reported for injections for inner ear gene transfection, but there was loss of vestibular function in the tested mice.211 ­

Injections or Bolus Administrations

Direct Inner Ear Injection

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Essentially, drug delivery mechanisms can be divi ded into those that bypass barriers to entry (such as direct inner ear injection and some NP carriers) and those that provide sustained drug concentrations, such as pumps or drug eluting compounds. Of course these mechanisms interact in that a higher concentration (whether by increase in applied drug concentration or increase in RWM permeability) will provide active drug for longer before elimination (i.e. prolonged exposure in the inner ear), and sustained release will result in higher concentrations if the RWM is not normally very permeable to the drug, i.e. increased concentration. Some technologies, such as cochlear implants can combine direct access with longer term drug delivery.

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Depot Injections Various polymers or depot compounds can be use to hold and elute drugs more slowly. The release of the drug is due to slow degradation of the material, drug diffusion or a combination of these. Polymers can be biostable or biodegradable, depending on the function required.

Hydrogels and Polymers Hydrogels are promising for short term (in the order of days) delivery of drugs, but not for chronic long-term

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delivery. The best clinically known hydrogel is probably Gelfoam. Gelfoam, and similar products, are biodegradable polymers, which have been used clinically, e.g. to deliver gentamicin212 on the RWM. It has been used also in many animal studies to deliver various substances, including BDNF.205 In the BDNF study, the BDNF effect was mainly noted in the basal cochlear region. Certainly other carriers have been shown to perform better for specific applications. For instance, comparing radioactive NT3 concentrations in he inner ear with delivery on Gelfoam pledgets versus alginate polymer microspheres, Noushi et al.206 found higher concentrations with the alginate. Alginate is a polysaccharide polymer, which can incorporate bioactive peptides, and is broken down into harmless metabolites. Another commonly used hydrogel is hyaluronic acid, an anionic nonsulfated glycosaminoglycan polysaccharide. A commercial preparation of this is Seprapack (Genzyme, Boston MA), which has been used to deliver dexamethasone205 and NAC213 to the inner ear via IT injection, and has been reported to reduce the hearing loss seen following cochlear implantation when used in this manner.214 Seprapack has been shown to provide a higher and more sustained concentration of dexamethasone in the cochlea after IT injection than injecting the dexamethasone alone drug alone.215 This has also been reported with other hydrogels.216 Various other hydrogels have been studied204,217 and found to be effective in delivering drug to the inner ear, including bioadhesive chitosans.218 Chitosan is a glucosamine polysaccharide, and have been used in animal experiments to deliver steroids219 and neomycin218 to the cochlea. Of particular interest are hydrogels that are temperature sensitive polymers. These can be injected as liquids, but transition into gels at body temperature, allowing sustained delivery. These types of hydrogels can be formulated from chitosan, or other polymers, e.g. Poloxamer. In animal models, Poloxamer provided a better concentration gradient along the cochlea from base to apex through its sustained release action than IT injections of drug alone.64

Microwicks Wicks act to channel externally applied drug or molecules to the RWW, i.e. they act as a refillable reservoir. One such example is the Silverstein Microwick, (Micromedics, Minnesota), made from polyvinyl acetate. This is introduced through a ventilation tube and placed in the round

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window niche. Whilst there do not appear to be any controlled studies comparing the Microwick to IT injection alone, it has been shown to be effective in various treat­ ment regimens. Gentamicin applied to the wick (10 mg/mL) was shown to control vertigo in 76.8% of Meniere’s disease patients,220 and with self-applied steroids also for Meniere’s disease an improvement was reported in 67% of subjects.221 As noted, it is unclear at this point if this method of delivery outperforms weekly IT injections.

Pumps Various types of pumps, primarily osmotic mini-pumps, have been used to deliver drugs over a longer time period to the cochlea. Previously the IntraEar Microcatheter (Durect, Cupertino, CA) was available as device for longer term delivery of drugs to the inner ear, and several publications showed efficacy of this system in delivering gentamicin and steroids to the inner ear.222 This has been used in the past in interesting “micro-dose” paradigms for gentamicin, in which it is claimed that vestibular function was not compromised, and perhaps even enhanced.101 This particular pump is no longer available commercially, and at present there are no micro-pumps that are available for widespread clinical use. Other types of pumps are reciprocating perfusion systems, which have zero net fluid volume change, through a process of pulsed drug injection, and perilymph fluid withdrawal, incorporating a recirculation element.223,224 By mixing perilymph with a reservoir of drug, these systems could potentially provide drug delivery for months or years. These can be programmed for complex dosing schedules. Because there is zero net fluid flow, there is less likelihood of spread of material to the CNS and contralateral ear. Other investigators have also proposed bone anchored subcutaneous micropumps, and shown proof of concept in rat models.225

Nanoparticles Various kinds of NPs have been studied for inner ear drug delivery, and numerous publications have shown in animal models that they can increase drug delivery and the sustained release of compounds to the inner ear, when compared to free drug alone. As of yet, however, none have been applied for clinical use in the inner ear, and their safety in the inner ear in humans has yet to be established, although most NPs seem safe in animal studies to date. NPs can increase transport across the RW, and increase

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Poly(lactic-co-glycolic acid) (PGLA): This is a biodegradable lactic acid/glycolic acid copolymer, which breaks down into naturally occurring metabolites. It is a versatile carrier, able to accept both hydrophilic and hydrophobic loads, and has been used for a wide variety of loads, including protein, steroids, antibiotics and nucleic acids.227,229 PGLA NPs are endocytosed and their packaging can modulate their release characteristics. They have been shown to distribute inside the cochlea when applied to the RWM, and could provide a way to provide sustained release inside the cochlea.230 They offer a safe and versatile way to deliver a variety of compound to the inner ear. Lipid nanocapsules: These contain a hydrophobic lipid (usually triglyceride) core, and a nonionic surfactant shell. They are cheap and very stable, for up to 1.5 years, and are very good for hydrophobic cargo. They have been used for a variety of purposes in the body, and in the inner ear to successfully deliver rolipram to the SGNs.231,232 They have been shown to penetrate the RWM and reach spiral ganglion cells in the rat, within 30 minutes of application.233 Polymersomes: Also known as polymeric vesicles, they are biomimetic structures that overcome the body’s natural defenses, are stable and their membrane properties can be configured for specific targets. They can accept both hydrophilic and hydrophobic loads, and drug delivery is through diffusion though the membrane, depending on a concentration gradient. They have been successfully used to deliver peptides to the cochlear nerve in rats.226

SPIONs: Magnetically active ferrous Fe3O4 particles can be coated with polymers such as PGLA, and made to enter the inner ear by external magnetic fields, by so called “magnetic injection” in guinea pigs, rats, and human temporal bones.234 Du et al. delivered dexamethasone to guinea pig cochleae using this technique.235 PGLA NPs encapsulated within iron oxide NPs can be made to cross the RWM when a magnetic field is applied. There are some safety concerns, however, with these ferrous particles, with reports of neural activity disruption even at low concentrations.236

Cochlear Implants as Drug Delivery Devices Cochlear implants enter the inner ear perilymph space anyway, and could be designed as a portal to deliver drugs.237,238 Primarily the interest in there use has been to preserve SGNs from any implantation trauma, and to prevent their ongoing degeneration. SGNS will degenerate without trophic support from hair cells, over time.190 If neurotrophic supporting factors such as NT3 or BDNF can be applied, however, SGNs survive, and these neuropeptides can be made to elute from CI coatings.239 These have to be continuously supplied, however, as their SGN supportive actions cease a few weeks after their supply ceases. There is some evidence, however, that electrical stimulation alone may provide some preservation of SGNs (see section above on neuropeptides). Steroids may also be supplied via the CI, and may reduce hearing loss from the trauma of implant insertion.240-243

REGENERATIVE AND GENE THERAPIES Cell Cycle Regulation It has long been appreciated that hair cell recovery can occur after cochlear damage in avian cochleae,244,245 but that this does not seem to happen spontaneously in the adult mammalian inner ear. In birds, hair cell regeneration can occur using two mechanisms, mitosis and transdifferentiation. Mitosis does not occur in adult mammals, but does in adult birds. In this process, actual hair cells divide, providing new hair cells. Another mechanism, which adult birds also exhibit, is transdifferentiation of supporting cells directly into hair cells. In general, cells in mammalian cochleae cells are prevented from reentering the mitotic cell cycle by various factors, such as the tumor suppressor gene p27kip1.246 Other cell cycle regulation genes such as p19/ink4d and Rb1 can also be manipulated to cause mammalian cochlear cells to divide, but the cells seem to enter programmed cell death soon after being produced.

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solubility, as many compounds have low aqueous solubility. NPs can also provide sustained release of their cargo drugs or compounds. They can also be coated with surface compounds such as peptides or antibodies, which allow them to target-specific structures. For instance, Zhang et al.226 used NP coated with TET1 peptide, and compared with non-TET1 coated particles, only TET1 coated ones were taken up by the cochlear nerve. However, this surface modification also changed the RWM permeability for the particles, and this may be a difficult additional challenge. All the NPs described below have been shown to cross the RWM, by both a paracellular and an intracellular route involving endocytosis (for a recent review, see ref.227). RWM transition efficiency decreases with increasing NP diameter.228 Interestingly, the OW maybe a site of entry for some NPs, allowing preferential treatment of vesti bular structures. Some of the major categories of NPs are reviewed below:

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In transdifferentiation, certain transcription factors bind to cell DNA and code for specific types of inner ear cells. One powerful such factor is Atoh 1 (also called Math1) that signals undifferentiated cells to become hair cells. Another important transcription factor is Sox 2. The Atoh1 factor is only one present in the developing cochlea, and but is turned off in the adult mammalian cochlea. Cells in the cochlea also exhibit lateral inhibition, in which local signals from neighboring cells prevent an overabundance of one cell type. With death of certain cell types, cell differentiation pathways are turned on in neighboring cells. This local control pathway is partly regulated by a receptor protein called Notch, and signals transcription factors Hes 1 and Hes 5.247,248 Cells in the adult organ of Corti are postmitotic, and there has been much research to try to induce these cells to proliferate. For an overview, the reader is directed to Raphael et al, and Okano et al.249,250 Cell phase transitions are controlled by cyclins and cyclin dependant kinases, which are controlled by many factors including the lnk4 cyclin-dependant inhibitor family, and Cip/Kip factors.251 It appears that p27kip1(also know as Cdkn1b) is highly expressed in supporting cells, but not in hair cells, and maybe a major reason for lack of regeneration in hair cells. For instance, mice lacking p27kip1 exhibit supernumerary cochlear hair cells and supporting cells, although function of the cochlea is disrupted by this overabundance.246,252 Raphaels’ group showed that inhibiting p27kip1 leads to division of the auditory epithelium, but not to the production of hair cells.33 Hence, inhibition of p27kip1 is not suffi­cient, by itself, for hair cell generation. Numerous other factors are known to be involved, including Rb, Rb12, Cdkn2d, Cdkn1a, and Cyclin D.250 The final step in cochlear development is the commitment of the prosensory cells to their hair or supporting cell fate. This is where Atoh 1 has been shown to be a crucial factor in driving cells toward a hair cell fate. Indeed Atoh 1 seems both necessary and sufficient to drive these cells in the early development phase toward hair cell differentiation. Atoh 1 is itself regulated through a complex mechanism that involves the transcription factor Sox2. Atoh 1 is not the only regulator of hair cell differentiation, however, as Notch signaling, through lateral inhibition, also determines the quantity of Atoh-1 positive cells that become hair cells; disrupting Notch signaling increases the number of hair cells.250 Despite these possibilities, generating actual new cells rather than transdifferentiating existing ones is important, as the population of supporting cells is not depleted, and it also allows the opportunity to insert

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large genes during into the genome, e.g. using retroviruses that is only possible during mitosis.

ROLE OF CELL DEATH AND CELL REPLACEMENT Many of the common ototoxic agents, such as aminoglycosides, cisplatinum and noise exposure, have their effect on hair cells by an apoptotic pathway, often by generating ROS (for review see section on cell death above, and ref.253). SGN cell death is often apoptotic as well, but occurs later than hair cell death in most insults. However, it can also occur by direct neuronal insult (as can happen from aminoglycosides), but more often from loss of neurotrophic support from hair cells.254

Neurotrophins In addition to their role in otoprotection, reviewed above, NTs have also been studied as growth factor proteins, and are involved in neurogenesis and synaptic and neuronal differentiation. They are generally produced by the innervation target cells, and then affect more central neurons. Four types of NTs have been identified in mammals. These include NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin 4 (NT-4). In the greater family of neurotrophic factors, other important proteins in the nervous system are glial-line derived neurotrophic factor [CDNF0, ciliary neurotrophic factor (CNTF) and fibroblast growth factor (FGF)]. These proteins activate extensive intracellular signaling pathways,190 and are known to be essential for the differentiation and survival of cochlear neurons. Hair cells secrete BDNF and NT-3, and these factors can act to stimulate formation of synapses with nerves attracted to the cells.255,256 Expression of these NTs by various cells (vestibular and cochlear), however, varies during developmental and mature phases. NT-3, e.g. is expressed by inner hair cells throughout deve­ lopment and adulthood, but not in outer hair cells in adulthood.190 This regulation of secretion of all the NTs, and expression of their target receptors is modified throughout the embryonal, early developmental and mature phases of the animal’s life in a highly complex and regulated manner. Null-mutation studies show that mice lacking BDNF only show a mild loss of type II SGNs, which innervate outer hair cells, primarily at the apical turn,257 whereas NT-3 null mutation mice show lack of inner and outer hair cell innervation, but primarily in the basal turn.258

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inhibitors such as gamma secretase inhibitors are small molecules that could be delivered to the inner ear through the round window, as proven by Mizutari et al.272 Other methods would be by the use of siRNA to block Hes gene product formation. These are exciting, as drug delivery to the inner ear is potentially easier to deliver than gene therapies, but at the expense of shorter term effects. Another small molecule that has exciting potential is DAPT, a molecule that inhibits gamma secretase and increases Atoh1 expression. Using this approach, various authors have shown generation of new hair cells in vitro273 and in vivo.274

GENE THERAPY



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When any of the four NT receptors are activated, they initiate a complex intracellular cascade that affects cell differentiation, proliferation, plasticity, axonal growth, and sometimes apoptosis (for review see references190,259,260). NT3 and BDNF have a vital role in maintaining SGNs in the mature cochlea, and their loss results in secondary degeneration of SGNs in various animal models, and the time course of the loss varies from species to species, occurring within a month in guinea pigs, and taking possi bly years in humans. Conversely, SGN loss can actually occur without hair cell loss,261,262 presumably by excitato xicity by overstimulation of the SGNs, e.g. by prolonged or intense acoustic stimulation. Many of the NTs have been found to be protective against ototoxic and acoustic trauma. However, they are relatively large molecules and difficult to get into the cochlea.

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Gene Therapy Vectors Gene therapy holds great potential for inner ear regeneration, and has been studied for decades. Some of the earliest work was from the Lalwani group.276 Various vectors have been proposed, and they differ in their ability to cross the round window, transfect various types of cells, the size of the gene they can carry, their potential pathogenicity, and the duration of transgene expression that occurs. In general, they can be divided into viral and nonviral vectors. Nonviral vectors include nonpackaged plasmids, or cationic liposomes or dendrimer carrier structures.275 While these induce less inflammation than viral vectors, they are generally less effective at gene transfection as well. Many different viruses are available for transfection in the inner ear, including adenovirus, adeno-associated virus (AAV), herpes simplex virus (HSV), vaccinia virus, lentivirus, and Sendai virus. For various reasons, among them concern about possible toxicity and unwanted transfection and pathogenicity in human use, and considering those most investigated to date, the most likely vectors for human use in the near term are adenovirus and AAV. ­

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Tissue differentiation in many tissues is controlled partly by the Notch signaling pathway,263 including in the inner ear, which controls progenitor cell differentiation into hair cells and supporting cells by a process of lateral inhi bition.264-266 Supporting cells are prevented from becoming hair cells, by Notch signaling from adjacent hair cells. Blocking Notch receptors diminishes activation of Hes1 and Hes5, which are a bHLH (basic helix-loop-helix) family of transcription factors and negative regulators of hair cell differentiation, and suppress Atoh 1.267 Notch inhibition could result in transdifferentiation of nonsensory cells to hair cells by increasing Atoh1 expression. Direct transfection of Atoh1 leading to cochlear hair cell generation directly has only been proven to be successful in embryo nic or newborn ears tissues.268-270 Izumikawa et al.271 used adenoviral transfection of Atoh 1 in adult damaged cochlea, and shown some hair cell differentiation, but it is unclear if these were cells that had recovered from trauma, or truly newly transdifferentiated hair cells.272 In a breakthrough recent study, Mizutari et al.272 were clearly able to restore hair cells damaged by noise, by transdifferentiation of supporting cells in adult mice, instead of newborn mice, by using a Notch inhibitor selected for potency from a range of gamma secretase inhi bitors. These mice showed both hair cell numbers increase and a functional increase in hearing ability. This may not be possible in long term deafened individuals when the Notch signaling pathway has returned to baseline levels, as opposed to the recently deafened animal model. Notch

The relative isolation of the cochlea makes it a difficult target for pharmacotherapy, but the same isolation makes it a very good candidate for gene therapy. Gene therapy can provide ongoing, perhaps lifetime, sources of molecules that are necessary for inner ear health, make the ear less susceptible to various insults by overexpressing protective factors, replace missing factors, down regulate or inhibit harmful factors, and potentially regenerate the inner ear. Gene therapy requires some kind of vector to deliver the gene cargo. The reader is referred to papers from Raphael’s group recent reviews on gene therapy.275



Small Molecule Regulation

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Adenovirus crosses the RWM well, and is expressed within 2 days across a wide variety of tissue types. However, its limitations are its possible toxicity and host immune responses to the adenovirus, and the transient gene expression.275 AAV shows long-term expression of genes, but can only carry relatively small genes, and is more difficult to transfect the inner ear with across the RWM.277 Among candidate vectors, AAV are unique in that the wild type virus does not cause any known human disease, and is probably the most promising viral vector for human use for small gene payloads. Genes can be delivered via the RWM using gel foam, partial digestion of the RWM,22 cochleostomy, injection through the RWM, or via infusion pumps. Other reported routes are via the semicircular canals and the ELS. For ears that are already deafened, cochleostomy openings may ensure efficient delivery with little additional risk to the inner ear, but for hearing ears, the risks of cochleostomy include hearing loss and damage, and other portals are more attractive. Most gene therapy to date has focused on hair cell regeneration, or on chronic delivery of NTs. For instance, Staecker et al.278 used a Herpes Simplex virus to deliver BDNF. After neomycin injection, the gene therapy group showed a 94.7% cell salvage rate, versus a 64.3% rate in control animals. Lalwani et al.279 showed a significant protective effect using an AAV to deliver BDNF, although the expression was very low, and far from the optimal dose. Since then, there have been several other studies showing effective gene transfer of NT-3280,281 showing protection against cisplatinum, as well as adenovirus mediated transfection of BDNF,282-284 which was protective against a variety of otologic insults. More recent work has shown that in addition to hair cell protection, NTs can induce auditory fiber growth toward the basilar membrane.285,286 Of particular interest are genes such as the X-linked inhibitor of apoptosis (XIAP), because they should be effec­ tive against many apoptotic processes. These genes have been studied by Wang’s group in mice, and found to show impressive protection against aging and noise,22,287,288 and shown by Cooper et al.289 when transfected with AAV, to prevent cisplatinum toxicity to hair cells. Once damage has occurred, the “holy grail” is hair cell and neuronal regeneration. So far, it seems that cochlear hair cell transdifferentiation from supporting cells is primarily effective in the neonatal period.290,291 A particularly well-studied gene is that Atoh/Math 1 gene, which

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seems particularly heavily involved in transdifferentiation of supporting cells into hair cells. Using a plasmid vector expressing Math 1 to transfect neonatal organ of Corti cultures resulted in supernumerary hair cells.292 A similar study using a human homologue of Math 1, with adenovirus transfection resulted in regeneration of vestibular neuroepithelium in vitro.293 Similarly, Kawamoto et al. delivered Math 1 to mature guinea pigs and showed production of ectopic hair cells that attracted some inner­ vation,294 and in ears deafened with kanamycin and ethacrynic acid; this treatment was also shown to produce some recovery of hearing suggesting functional regrowth.271 However, in general the effects of transfection of Atoh 1 into wild type animals (as opposed to transgenic mice models overexpressing Atoh 1) have shown limited success in the mature cochlea, although they seem to be more successful in vestibular regeneration.275 Another exciting application of gene therapy is in hereditary disease. In these cases, hair cell regeneration is likely to lead to renewed death of the hair cells, as the underlying defect is still present. However, replacement of the faulty gene or supplementation may be possible. An example of this is that hearing was successfully restored in VGLUT3 mice mutants with AAV1-VGLUT3 gene delivery in knockout mice, improving hearing thresholds.295 Certainly, there are numerous obstacles to overcome before gene therapy becomes a reality. Not least of these are safety concerns, both with the pathogenicity and toxi­ city of the vector, and of uncontrolled expression of the gene. Genes may migrate to nontarget tissues, e.g. Lalwani et al.276 for AAV, and Stover et al.296 showed expression of the Adenoviruses in the contralateral cochlea.

RNA Therapies At the interface of peptide and gene incorporation strate­gies are strategies that involve the RNA interface. RNA strate­ gies involve inactivating faulty messenger RNA (mRNA) by particles called small interfering RNAs, (siRNA), made from cleaving double strand RNA and incorporating them in a protein complex.297,298 These siRNAs are 20–30 nucleotides in length, and can “silence” specific genes by binding to mRNA to inactivate it. In the serum, siRNAs have a short life span, but in the cochlea, their life span maybe more prolonged. They are particularly suited to silencing aberrant mRNA in dominant-negative types of disorders. The GJB2 protein, e.g. has been silenced by this mechanism

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Stem Cell Therapies

CONCLUSION

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This is an exciting time in inner ear molecular therapy. The ability to target the inner ear directly through the RWM and OW will increase even further with new carriers that allow drugs to cross these windows more efficiently, and with little risk to residual inner ear function. These carriers and vectors will also allow us to manipulate the pharmacokinetics of drugs to target various tissues, and avoid injury to other sensitive tissues. They will also allow us to get classes of drugs into the inner ear that currently are unable to access it efficiently. We are only beginning to understand the complexities of inner ear homeostasis, and the actions of various drugs in the inner ear, and indeed the actions of various diseases in the ear. This may allow us to develop new types of drugs to specifically address deficits caused by specific otologic diseases. Some drugs may prove to be nonspeci fic protectants against a wide variety of insults. One such insidious damaging factor is simple aging. It may be possible to make the inner ear generally more “robust” to any inner ear insult, so protecting against noise, ototoxicity, and other traumas for a lifetime. Of course, the most exciting development would be the ability to completely regenerate healthy, functioning and stable inner ear tissue in damaged ears. Significant strides have been made in this area, but there are numerous hurdles, both scientific, safety related and regulatory before such treatments become feasible. These regenerative treatments could be combined with artificial implants to improve function of the implants, or perhaps even to improve function beyond human “normal” auditory and vestibular abilities.

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Although stem cell therapies are not strictly molecular therapies, they will be briefly reviewed here. Stem cells are defined by their ability to proliferate into multiple distinct cell lines. Stem cell research overcame a huge hurdle in 2006, when it was demonstrated that expressing only 4 genes (Sox2, Pou5fl, Klf4, and Myc) was sufficient to induce many adult cell types to become pluripotent,302,303 avoiding the need for embryonal stem cells. Ito et al.304 showed, as early as 2001, that hippocampal cells injected into the neonate rat cochlea took on morphologies similar to cochlear cells. Work since then has shown that some stem/progenitor cells are present in the mammalian inner ear, but after birth, their numbers drop rapidly.250 Various authors250 have shown that isolated stem cells can be made to develop into hair cell like structures with the right growth and transcription factors, but the yields have been low, and much still is unknown about this process. While stimulating endogenous stem cells to differentiate into hair cells, neural cells and supporting cells would be the ideal solution, the population of such cells is likely very low in the adult inner ear. This has led to investigations into the use of transplan ted stem cells into the inner ear. Numerous authors have investigated various types of stem cell transplants into the inner ear, and have shown that they can develop into neural cells, supporting cells and hair cells, but the yield is low and the cells population seems to fall within several weeks. The functional status of the cells is also not clear in most reports. It is also difficult to get cells into various inner ear compartments, because of the tight junctions between cells to maintain the electrochemical gradient in the scala media. The high potassium in the scala media is also likely toxic to cells. Cells must also attract innervation once diffe rentiated into hair cells. Also, in many ears, both the hair cells and neural cells have been lost, and both would have to be replaced in a coordinated manner to achieve auditory function. Another target, perhaps more advanced in terms of research, has been replacement of spiral ganglion cells

using stem cells. Many investigators have successfully derived neural cells from implanted stem cells, and shown that they will extend processes toward the organ of Corti. To date, no study has clearly shown that these cells will sense auditory function (for review see ref. 250) The relative accessibility of the spiral ganglion makes this a pro mising area of research however. Other targets have been to implant cells that secrete various neurotrophic or growth factor that maintain health of the inner ear, or promote repair. This is another promising approach, and one that may be functionally easier to achieve, and may help improve function of devices such as cochlear implants. ­

in the mouse inner ear.299 In other uses siRNA therapy has been used in the rat to prevent cisplatin ototoxicity.300,301 Other uses have been in the inhibition of NOX3, which is one of the primary sources of ROS in the cochlea. siRNA directed against NOX3 prevented SGN and HC damage from cisplatinum, for instance.301

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264. Brooker R, Hozumi K, Lewis J. Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear. Development. 2006;133(7):1277-86. 265. Lanford PJ, Lan Y, Jiang R, et al. Notch signalling pathway mediates hair cell development in mammalian cochlea. Nat Genet. 1999;21(3):289-92. 266. Kelley MW. Regulation of cell fate in the sensory epithelia of the inner ear. Nat Rev Neurosci. 2006;7(11):837-49. 267. Zine A, Aubert A, Qiu J, et al. Hes 1 and Hes 5 activities are required for the normal development of the hair cells in the mammalian inner ear. J Neurosci. 2001;21(13):4712-20. 268. Doetzlhofer A, Basch ML, Ohyama T, et al. Hey 2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti. Dev Cell. 2009;16(1):58-69. 269. Gubbels SP, Woessner DW, Mitchell JC, et al. Functional auditory hair cells produced in the mammalian cochlea by in utero gene transfer. Nature. 2008;455(7212):537-41. 270. White PM, Doetzlhofer A, Lee YS, et al. Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature. 2006;441(7096):984-7. 271. Izumikawa M, Minoda R, Kawamoto K, et al. Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals. Nat Med. 2005;11(3):271-6. 272. Mizutari K, Fujioka M, Hosoya M, et al. Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron. 2013;77(1):58-69. 273. Lin V, Golub JS, Nguyen TB, et al. Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles. J Neurosci. 2011;31(43):15329-39. 274. Hori R, Nakagawa T, Sakamoto T, et al. Pharmacological inhibition of Notch signaling in the mature guinea pig cochlea. Neuroreport. 2007;18(18):1911-4. 275. Fukui H, Raphael Y. Gene therapy for the inner ear. Hear Res. 2013;297:99-105. 276. Lalwani AK, Walsh BJ, Reilly PG, et al. Development of in vivo gene therapy for hearing disorders: introduction of adeno-associated virus into the cochlea of the guinea pig. Gene Ther. 1996;3(7):588-92. 277. Jero J, Mhatre AN, Tseng CJ, et al. Cochlear gene delivery through an intact round window membrane in mouse. Human Gene Ther. 2001;12(5):539-48. 278. Staecker H, Kopke R, Malgrange B, et al. NT-3 and/or BDNF therapy prevents loss of auditory neurons following loss of hair cells. Neuroreport. 1996;7(4):889-94. 279. Lalwani AK, Jero J, Mhatre AN. Current issues in cochlear gene transfer. Audiol Neuro-otol. 2002;7(3):146-51. 280. Bowers WJ, Chen X, Guo H, et al. Neurotrophin-3 transduction attenuates cisplatin spiral ganglion neuron ototoxicity in the cochlea. Mol Ther. 2002;6(1):12-8. 281. Chen X, Frisina RD, Bowers WJ, e al. HSV amplicon-mediated neurotrophin-3 expression protects murine spiral ganglion neurons from cisplatin-induced damage. Mol Ther. 2001;3(6):958-63. 282. Yagi M, Magal E, Sheng Z, et al. Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor. Hum Gene Ther. 1999;10(5):813-23.

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283. Suzuki M, Yagi M, Brown JN, et al. Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity. Gene Ther. 2000;7(12):1046-54. 284. Yagi M, Kanzaki S, Kawamoto K, et al. Spiral ganglion neurons are protected from degeneration by GDNF gene therapy. J Assoc Res Otolaryngol. 2000;1(4):315-25. 285. Wise AK, Fallon JB, Neil AJ, et al. Combining cell-based therapies and neural prostheses to promote neural survival. Neurotherapeutics. 2011;8(4):774-87. 286. Wise AK, Hume CR, Flynn BO, et al. Effects of localized neurotrophin gene expression on spiral ganglion neuron resprouting in the deafened cochlea. Mol Ther. 2010;18(6): 1111-22. 287. Wang J, Menchenton T, Yin S, et al. Over-expression of X-linked inhibitor of apoptosis protein slows presbycusis in C57BL/6J mice. Neurobiol Aging. 2010;31(7): 1238-49. 288. Wang J, Tymczyszyn N, Yu Z, et al. Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice. Gene Ther. 2011;18(6): 560-8. 289. Cooper LB, Chan DK, Roediger FC, et al. AAV-mediated delivery of the caspase inhibitor XIAP protects against cisplatin ototoxicity. Otol Neurotol. 2006;27(4):484-90. 290. Kelly MC, Chang Q, Pan A, et al. Atoh1 directs the formation of sensory mosaics and induces cell proliferation in the postnatal mammalian cochlea in vivo. J Neurosci. 2012;32(19):6699-710. 291. Liu Z, Dearman JA, Cox BC, et al. Age-dependent in vivo conversion of mouse cochlear pillar and Deiters’ cells to immature hair cells by Atoh1 ectopic expression. J Neurosci.: The Official Journal of the Society for Neuroscience. 2012;32(19):6600-10. 292. Zheng JL, Gao WQ. Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears. Nat Neurosci. 2000;3(6):580-6. 293. Shou J, Zheng JL, Gao WQ. Robust generation of new hair cells in the mature mammalian inner ear by adenoviral expression of Hath1. Mol Cell Neurosci. 2003;23(2): 169-79. 294. Kawamoto K, Ishimoto S, Minoda R, et al. Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo. J Neurosci. 2003;23(11):4395-400. 295. Akil O, Seal RP, Burke K, et al. Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy. Neuron. 2012;75(2):283-93. 296. Stover T, Yagi M, Raphael Y. Transduction of the contralateral ear after adenovirus-mediated cochlear gene transfer. Gene Ther. 2000;7(5):377-83. 297. Behlke MA. Progress towards in vivo use of siRNAs. Mol Ther. 2006;13(4):644-70. 298. Hildebrand MS, Newton SS, Gubbels SP, et al. Advances in molecular and cellular therapies for hearing loss. Mol Ther. 2008;16(2):224-36. 299. Maeda Y, Fukushima K, Nishizaki K, et al. In vitro and in vivo suppression of GJB2 expression by RNA interference. Hum Mol Genet. 2005;14(12):1641-50.

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302. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluri potent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861-72. 303. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76. 304. Ito J, Kojima K, Kawaguchi S. Survival of neural stem cells in the cochlea. Acta Otolaryngol. 2001;121(2):140-2.





300. Mukherjea D, Jajoo S, Whitworth C, et al. Short interfering RNA against transient receptor potential vanilloid 1 attenuates cisplatin-induced hearing loss in the rat. J Neurosci. 2008; 28(49):13056-65. 301. Mukherjea D, Jajoo S, Kaur T, et al. Transtympanic administration of short interfering (si)RNA for the NOX3 isoform of NADPH oxidase protects against cisplatin-induced hearing loss in the rat. Antioxid Redox Signal. 2010;13(5):589-98.

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CHAPTER Anatomy and Physiology of the Facial Nerve

36

Ruwan Kiringoda, John K Niparko, Lawrence R Lustig

INTRODUCTION The facial nerve is uniquely complex in terms of its form, function, and physiology. The facial nerve, the seventh cranial nerve, is involved in congenital anomalies and degenerative disorders and affected by a range of acquired pathology, from infectious to neoplastic conditions. A thorough understanding of its embryology, anatomy, and physiology enables the physician to accurately diagnose and treat disorders of the facial nerve.

EMBRYOLOGY Intratemporal Development The facial nerve (Figs. 36.1A to C and Table 36.1) begins to form near the end of the first month of gestation. A collection of neural crest cells gives rise to the acousticofacial primordium that develops adjacent to the primordial inner ear, the otic placode, and eventually gives rise to the facial and acoustic nerves.1 As the facial and acoustic portions differentiate, the otic placode invaginates, forming the otocyst, a precursor to the eventual membranous labyrinth of the inner ear. Anlagen of the geniculate ganglion appears early in the second month of gestation. Adjacent to the geniculate ganglion, the distal segment of the acousticofacial primordium differentiates into caudal and rostral trunks, which represent the eventual main trunk of the facial nerve and chorda tympani nerve, respectively. The complex, tortuous course of the facial nerve and chorda tympani is explained by their separate origin and subsequent intersection.2 During the sixth week of gestation, the motor division of the facial nerve establishes its

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position in the middle ear between the membranous labyrinth (an otic placode structure) and the developing stapes (a second arch structure). During this time, the chorda tympani nerve becomes associated with the trigeminal nerve, which carries the chorda tympani on its way to the tongue via the lingual nerve. The greater superficial petrosal nerve, which carries preganglionic parasympathetic fibers toward the pterygopalatine ganglion, also develops during this time period.3 Anatomic relationships of the facial nerve are established by the end of the second month; when the cartilaginous otic capsule forms around the membranous labyrinth, while the facial nerve travels in a sulcus within the cartilaginous capsule. The otic capsule begins to ossify at the end of the fourth month, while the fallopian canal, the bony canal that transmits the facial nerve through the temporal bone, begins ossification in the fifth gestational month, in a process that is not complete until several years after birth.3-5 Formation of the fallopian canal occurs when two periosteal shelves of bone surround the facial nerve. Fusion of the shelves occurs in an anterior to posterior direction, concluding postpartum in the region of the oval window.6 Incomplete development of the fallopian canal in this model represents normal anatomic variation, rather than a congenital anomaly. These natural dehiscences may contribute to facial palsies associated with otitis media or barotrauma, while also placing the facial nerve at risk during middle ear surgery.7-9

Extratemporal Development During the sixth gestational week through the end of the second gestational month, all five divisions of the

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A

B

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Figs. 36.1A to C: A schematic illustration demonstrating the embryology of the facial nerve. (A) The location of the facial nerve in the developing embryo is shown in relation to the other impor­ tant nerves in the head and neck. The trigeminal nerve (5) supplies the first pharyngeal arch and has three branches: the ophthalmic, maxillary, and mandibular. The nerve of the second arch is the facial nerve (7); that of the third is the glossopharyngeal nerve (9). The musculature of the fourth arch is supplied by the superior laryngeal branch of the vagus nerve (10), and that of the sixth arch by the recurrent branch of the vagus nerve. (B) The location of the second branchial arch, giving rise to the main trunk of the facial nerve, is shown in relation to the other branchial arches. (C) Other derivatives of the second branchial arch are shown, which help explain the complex innervation pattern of the facial nerve. Labels I-V represent the first through fifth branchial arch deriva­ tives, respectively. Source: Adapted with permission from Sadler TW. Langman’s Medical Embryology, fifth edition. Baltimore: Lippincott, Williams and Wilkins; 2006.

C

Postnatal Development

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At birth, the facial nerve is located just beneath the skin near the mastoid tip as it emerges from the temporal bone, and is vulnerable to the postauricular incision in a young child. As the mastoid tip forms and elongates during childhood however, the facial nerve assumes its more medial and protected position. Individual axons of the facial nerve also undergo myelination until the age of 4 years, an important consideration during electrical testing of the nerve during this time period.12 ­



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extratemporal nerve—the temporal, zygomatic, buccal, mandibular, and cervical branches—are present. With time, interconnections develop between peripheral branches of the facial nerve, while communications also develop between extratemporal facial nerve branches and branches of the cervical plexus and trigeminal nerve.10,11 During the third month, the parotid bud enlarges and engulfs the facial nerve.10 Gland ductules grow between the developing nerve branches, resulting in myriad connections between the superficial and deep portions of the gland, without any discrete capsule separating these two aspects. The facial muscles (Fig. 36.2), developing independently, are formed at 7–8 weeks’ gestation and must be innervated by the distal facial nerve branches or else the muscle will degenerate, although this critical time period before degeneration is not currently known. By the end of the third gestational month, a majority of the facial musculature is identifiable and functional.5

CENTRAL NEURONAL PATHWAYS Supranuclear Pathways The primary somatomotor cortex of the facial nerve, controlling the complex motor function of the face, is located in the precentral gyrus, corresponding to Brodmann areas

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Table 36.1: Facial nerve development

Gestational month

Development

1

Acousticofacial (AF) primordium gives rise to both the facial and acoustic nerves

2

Geniculate ganglion develops Caudal trunk of AF primordium develops into main trunk of facial nerve (FN) Rostral trunk of AF primordium develops into chorda tympani nerve Motor division of FN establishes position between labyrinth and stapes Chorda tympani nerve becomes associated with trigeminal nerve Greater superficial petrosal nerve develops Five extratemporal branches develop Facial muscles develop independently

3

FN elongates Fallopian canal develops, continuing through birth Parotid bud engulfs extratemporal FN Facial musculature is identifiable and functional

4-Birth

FN elongates Fallopian canal continues to develop

Postnatal

FN axon myelination, continuing through age 4 years Lateral location of extratemporal FN gradually medializes under developing mastoid tip

4, 6, and 8 (Fig. 36.3). Neural projections from this area making up the corticobulbar tract descend through the internal capsule and then through the pyramidal tracts within the basal pons. In the caudal pons, most of the facial nerve fibers cross the midbrain to reach the contralateral facial nucleus. A small number of facial nerve fibers innervate the ipsilateral facial nucleus, a majority of which are destined for the temporal branch of the nerve.13 This innervation pattern explains why central nervous system lesions spare the forehead muscle, since they receive input from both cerebral cortices, whereas peripheral lesions involve all branches of the facial nerve.14-17 More recent somatotopic primate studies suggest an alternate explanation: upper facial motor neurons receive little direct cortical input, while lower facial muscles depend heavily on cortical innervation. Thus, the foreheadsparing aspect of cortical lesions may in fact be explained by this regions relatively lower dependence on cortical innervation.18 In addition to these voluntary neural projections to the facial nerve, there is also an extrapyramidal cortical input to the facial nucleus from the hypothalamus, the globus

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Fig. 36.2: An adaptation of Sir Charles Bell’s classic illustration of the muscles of facial expression, with the muscles labeled. Source: Reproduced from Bell C. Essays on the Anatomy of Facial Expression, 2nd edition. London: Murray; 1824.

Fig. 36.3: A schematic illustration of the complete pathway of the motor division of the facial nerve. Source: Redrawn with permission from Sadler TW. Langman’s Medical Embryology, 12th ed. Baltimore: Lippincott Williams & Wilkins; 2012.

pallidus, and the frontal lobe, all of which control involuntary facial expression associated with emotion. Additional projections to the facial nuclei from the visual system are involved in the blink reflex. Projections from the trigeminal nerve and nuclei contribute to the corneal reflex, whereas those from the auditory nuclei help the eye close involuntarily in response to loud noises.

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Otology/Neurotology/Skull Base Surgery The special visceral afferent fibers, which also form a portion of the chorda tympani nerve, receive input from the taste buds of the anterior two-thirds of the tongue, as

Facial Nucleus and Brainstem

Nervus Intermedius

Function

Branchial motor

Muscles of facial expression Posterior belly of the digastric muscle Stylohyoid muscle Stapedius muscle

Visceral motor

Salivation—lacrimal, submandi bular, and sublingual glands Nasal mucosa or mucous mem brane

General sensory

Sensory to auricular concha External auditory canal Tympanic membrane

Special sensory

Chorda tympani nerve—taste to anterior two-thirds of tongue



The nervus intermedius, or Wrisberg’s nerve, mediates taste, cutaneous sensation of the external ear, proprioception, lacrimation, and salivation. The nervus intermedius exits the brainstem adjacent to the motor branch of the facial nerve (Table 36.2 and Fig. 36.5). The nerve commonly clings to the adjacent cochleovestibular nerve complex rather than the facial nerve and crosses back to the seventh nerve as it approaches the internal auditory meatus.19 General visceral efferent fibers of the nervus intermedius are preganglionic parasympathetic neurons that innervate the lacrimal, submandibular, sublingual, and minor salivary glands. The cell bodies of these nerves arise in the superior salivatory nucleus and join the facial nerve after it has passed the abducens nucleus. They travel together until reaching the geniculate ganglion in the temporal bone. At this point, the greater superficial petrosal nerve branches off, composed of neurons destined for the pterygopalatine ganglion. The greater superficial petrosal nerve ultimately innervates the lacrimal, minor salivary, and mucosal glands of the palate and nose. Remaining fibers form part of the chorda tympani nerve, proceed to the submandibular ganglion, and eventually proceed to the submandibular and sublingual salivary glands.

Table 36.2: Subdivisions and functions of the facial nerve

Facial nerve subdivision

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The efferent projections from the facial motor nucleus emerge dorsomedially to form a compact bundle that loops over the caudal end of the abducens nucleus beneath the facial colliculus or internal genu (or turn). The neurons then pass between the facial nerve nucleus and the trigeminal spinal nucleus, emerging from the brainstem at the pontomedullary junction (Fig. 36.4).

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Fig. 36.4: The anatomy of the facial nerve (CN VII) and cochleo­ vestibular nerve (CN VII) as they exit the brainstem at the level of the pontomedullary junction. Source: Redrawn with permission from Sadler TW. Langman’s Medical Embryology, 12th ed. Baltimore: Lippincott Williams & Wilkins; 2012.

Fig. 36.5: The anatomy of the visceral motor portion of the facial nerve, making up the nervus intermedius, or nerve of Wrisberg. The preganglionic, parasympathetic portions of this nerve have cell bodies located in the abducens nucleus. From there they travel toward the geniculate ganglion in the temporal bone, located at the first genu of the facial nerve on the floor of the middle cranial fossa. Fibers from this nerve are destined to innervate the lacrimal gland, minor salivary glands, and mucosal glands of the palate and nose. Source: Redrawn with permission from Sadler TW. Langman’s Medical Embryology, 12th ed. Baltimore: Lippincott Williams & Wilkins; 2012.

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Chapter 36: Anatomy and Physiology of the Facial Nerve well as the hard and soft palates (Fig. 36.6). The sensory afferents for taste have their cell bodies in the geniculate ganglion and will eventually synapse in the medulla, in the nucleus solitarius. The general sensory afferent neurons of the nervus intermedius are responsible for cutaneous sensory infor­ mation from the external ear canal and postauricular region. These cutaneous sensory fibers enter the spinal trigeminal tracts without synapsing in the geniculate ganglion.

Cerebellopontine Angle The facial nerve leaves the brainstem at the pontomedullary junction, where it lies in close approximation to the vestibulocochlear nerve (see Fig. 36.4). This intimate relationship takes on critical importance when lesions arise in the region of the cerebellopontine angle (CPA), a common location for central nervous system tumors. In this location, the facial nerve is placed in jeopardy both during the growth of the tumor and during attempted surgical resection in this area. During its lateral course through the CPA and internal auditory canal (IAC), the relative positions of the facial and cochleovestibular nerves change by rotating 90°.20 In the CPA, the facial nerve is covered with pia,

621

is bathed in cerebrospinal fluid, and is devoid of epineurium, leaving it susceptible to manipulation trauma during intracranial surgery. Lesions involving the CPA commonly include vestibular schwannomas, meningiomas, and primary cholesteatomas. Larger lesions can cause compression of the CPA that leads to deficits affecting more than just the vestibulocochlear nerve, involving the fifth, then ninth, tenth, and eleventh cranial nerves. Also of note, the presence of coursing arteries in proximity to the facial nerve at the CPA has been implicated as one cause of hemifacial spasm; treatment with microvascular decompression at the facial nerve root is a well described.21

INTRATEMPORAL NERVE PATHWAYS After traversing the CPA, the facial nerve enters the temporal bone along the posterior face of the petrous bone. Within the temporal bone, the facial nerve successively passes through four regions before its exit out of the stylomastoid foramen: (1) the IAC, (2) the labyrinthine segment, (3) the intratympanic segment, and (4) the descending segment (Figs. 36.7 to 36.9). From the lateral end of the IAC to its exit out the stylomastoid foramen, the nerve travels approximately 3 cm within the fallopian canal.

Internal Auditory Canal The facial nerve enters the temporal bone along the poste­ rior face of the petrous bone, piercing the internal auditory meatus. At the lateral end of the IAC, the traverse crest divides the IAC into superior and inferior portions. The superior portion is in turn further divided by the smaller and more laterally located vertical crest or “Bill’s bar”. At this lateral portion of the IAC, the anatomy is most consis­ tent: The superior portion is occupied by the facial nerve anteriorly and the superior vestibular nerve posteriorly (Fig. 36.8). Within the IAC, the dural covering of the facial nerve transitions to epineurium.

Labyrinthine Segment

Fig. 36.6: The anatomy of the special sensory component of the facial nerve, comprising the chorda tympani nerve. Source: Redrawn with permission from Sadler TW. Langman’s Medical Embryology, 12th ed. Baltimore: Lippincott Williams & Wilkins; 2012.

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At the lateral portion of the IAC, the facial nerve pierces the meatal foramen to enter the labyrinthine segment. This portion of the nerve runs beneath the middle cranial fossa, passing posterior to the cochlea and anterior and medial to the ampulated ends of the horizontal and superior semi­circular canals. The distance between the facial nerve and basal turn of the cochlea that is less than the standard size of the smallest diamond drills (0.6 mm) in

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Fig. 36.7: The intratemporal divisions of the facial nerve. After passing through the internal auditory meatus on the posterior face of the petrous temporal bone, the nerve enters its canalicular seg­ ment, as it traverses between the cochlea and the vestibular laby­ rinth. After making its first genu (bend) at the genicular ganglion, it becomes the tympanic segment, coursing through the middle ear space, just superior to the oval window. It then makes its sec­ ond major genu at the level of the horizontal semicircular canal, and becomes the vertical or descending segment. After passing through the stylomastoid foramen, it becomes extracranial.

the vast majority of patients, underscoring the importance of meticulous dissection of the facial nerve during middle cranial fossa approaches.22The geniculate ganglion is considered the end of the labyrinthine segment of the nerve and lies just superior to the nerve. Arising from the geniculate ganglion is the greater superficial petrosal nerve, containing preganglionic parasympathetic fibers destined for the lacrimal gland, as well as for the nasal and palatine mucosal glands. The nerve also contains some minor taste neurons that supply the posterior palate. The labyrinthine segment is further notable in that it is the narrowest portion of the fallopian canal, where it averages < 0.7 mm in diameter, occupies the canal to the greatest proportional extent, and is lined by a fibrous annu­lar ligament.23 As a result, it is believed that infections or inflam­mations causing edema of the facial nerve within this region can lead to temporary or permanent paralysis of the nerve, such as in Bell palsy.

Fig. 36.8: A stylized representation of the lateral aspect of the internal auditory canal. The facial nerve lies at the most anterior and superior location at this level.

nerve, so called because it travels within the middle ear space. This portion of the nerve is approximately10 mm long. Landmarks for the nerve at this location include the cochleariform process, which gives rise to the tensor tympani muscle, and the “cog”, a small bony prominence projecting from the roof of the epitympanum. The facial nerve then travels posteriorly, just superior to the oval window and stapes. The nerve then curves inferiorly at its second genu, just posterior to the oval window, pyramidal process, and stapedial tendon, and anterior to the horizontal semicircular canal. It is this portion of the nerve that is most susceptible to injury during surgery because processes such as cholesteatoma frequently erode the bone covering the facial nerve in this region, leaving it precariously exposed. In addition to bony dehiscence from pathology, natural fallopian canal dehiscences have also been described in cadaver specimens, a majority of which occurred in the tympanic segment. In more than 80% of cases, the dehiscences involved the portions of the canal adjacent to the oval window.24

Tympanic Segment

Vertical, Descending, or Mastoid Segment

At the geniculate ganglion, the facial nerve makes its first genu and becomes the tympanic segment of the facial

After the second genu, the nerve traverses the synonymously named vertical, descending, or mastoid segment

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Chapter 36: Anatomy and Physiology of the Facial Nerve

A

B

C

Figs. 36.9A to C: Histologic cross sections of the facial nerve at three points along its course within the temporal bone. Proximally within the temporal bone at the level of the internal auditory canal (A), the individual nerve fascicles are not defined, and nerve ele­ ments appear homogeneous. (B) As the nerve proceeds through the tympanic segment and (C) at the level of the stylomastoid fora­ men, individual nerve fascicles become increasingly defined.

en route to the stylomastoid foramen. As the facial nerve descends inferiorly in this portion, it gradually assumes a more lateral position. Important branches of the nerve in this segment include the nerve to the stapedius muscle and the chorda tympani nerve. As it arises from the facial nerve, the chorda tympani nerve makes an approximately 30° angle and delineates a triangular space known as the “facial recess”, an important surgical route of entry into the middle ear space. In its most inferior portion, the facial nerve takes on a close proximity to the digastric ridge and muscle, where the nerve is consistently medial and anterior to these structures. On exiting the stylomastoid foramen, the nerve becomes encased in the thick fibrous tissue of the cranial base periosteum and digastric muscle. Although the facial nerve most commonly descends in its vertical segment as a single nerve, bifurcations, trifurcations, and hypoplasia of the facial nerve have been found within the mastoid segment.7 In addition, the chorda

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tympani nerve has been noted to arise from the facial nerve anywhere from the stylomastoid foramen to the geniculate ganglion.25

Peripheral Facial Nerve Anatomy The facial nerve exits the skull base through the stylomastoid foramen, between the mastoid tip laterally and the styloid process medially (Fig. 36.10). At the stylomastoid foramen, the facial nerve passes into the parotid gland, typically as a single large trunk. The nerve then divides within the parotid gland into its temporofacial and cervicofacial branches. Rarely, this division can occur within the temporal bone and exit the stylomastoid foramen as separate branches. Within the parotid gland, the nerve can assume nume­ rous configurations, with frequent anastomoses between branches. However, generally five main branches of the nerve can be identified: (1) the temporal, (2) the zygomatic,

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Fig. 36.10: A portion of an illustration from Sir Charles Bell, demon­ s­trating the exit of the facial nerve from the stylomastoid foramen. Source: Reproduced from Bell C. The Nervous System of the Human Body. Longman; 1830.

(3) the buccal, (4) the mandibular, and (5) the cervical. The temporal branch innervates the frontalis muscle, which allows for the voluntary raising of eyebrows. The zygomatic branch innervates the orbicularis oculi muscle and is critical for proper eye closure. The buccal nerve innervates the buccinator and orbicularis oris, allowing for proper mouth closure and cheek muscle activity. The mandibular branch innerves the platysma. The posterior auricular nerve, arising just after the exit of the facial nerve from the stylomastoid foramen, sends branches to the occipitalis muscle posteriorly on the skull.

FACIAL NERVE PHYSIOLOGY Anatomic Considerations The facial nerve trunk consists of approximately 10,000 nerve fibers, approximately 7000 of which are myelinated motor fibers. The facial nerve sheath consists of several layers. The endoneurium, closely adherent to the layer of Schwann cells of the axons, surrounds each nerve fiber. The perineurium, which is the intermediate layer surrounding groups of fascicles, provides tensile strength to the nerve and is believed to represent the primary barrier to the spread of infection. The outermost layer of the nerve is the epineurium. This outer layer contains the vasa nervorum, which provides the blood supply to the nerve.

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Fig. 36.11: A model of graded neural injury that details clinical– pathologic classifications. Microanatomic changes in cranial nerve injury are demonstrated in cross section. The potential for approxi­ mate axonal regeneration across the site of injury is dictated prin­ cipally by the status of connective tissue elements.

Classification of Facial Nerve Degeneration If the facial nerve is injured, various degrees of injury may result.26 The most widely used model of clinicopathologic classification of nerve injury is the classification originally proposed by Sunderland (Fig. 36.11): 1. First-degree injuries are characterized by compression causing the blockage of axoplasmic flow (neuropraxia). There are no morphologic changes. Although an action potential cannot be propagated across the lesion site, a stimulus applied distal to the lesion will conduct normally to produce an evoked response. Complete recovery is expected. 2. Second-degree injuries entail axonal and myelin disruption distal to the injury site as a result of the pro­ gression of a first-degree injury (axonotmesis). Wallerian

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Chapter 36: Anatomy and Physiology of the Facial Nerve degeneration occurs distal to the site of injury, which eliminates the propagation of an externally applied stimulus. Axon regeneration occurs at 1 mm per day; near complete recovery is expected, except in fibers that suffer progression to third degree injury. 3. Third-degree injuries involve complete disruption of the endoneurial tube, including the axon plus its surround­ ing myelin and endoneurium (neurotmesis). Axonal regrowth may occur, but is susceptible to synkinesis, the contraction of multiple muscle fibers simultaneously with voluntary movement, e.g. mouth movement with eye closure. 4. Fourth-degree injuries entail the disruption of the perineurium (partial transection). Profound long-term weak­ness is expected. 5. Fifth-degree injuries entail the disruption of the epine­ urium (complete transection). No recovery is expected without intervention. 6. Sixth-degree injuries, a proposed addition to the Sunderland classification by later authors, take into account the observed patterns of blunt and penetrating injuries of the nerve. These injuries are characterized by normal function through some fascicles and varying degrees of injury (first-degree through fifth-degree injuries), differentially involving fascicles across the nerve trunk. Central to the Sunderland classification is the notion that axonal recovery depends on the integrity of the connective tissue elements of the nerve trunk. This model predicts a high likelihood for the complete recovery of peripheral innervation when endoneurial tubules remain intact to support reinnervation, as is the case with first- and seconddegree injuries. In contrast, disruption of the endoneurium—a third-degree injury or worse in this model— increases the likelihood of irreversible axonal injury and aberrant patterns of regeneration. An example of abnormal neural regrowth is “crocodile tears”, or increased lacrimation associated with eating. It occurs when efferent fibers normally targeted to travel with the chorda tympani nerve to the submandibular and sublingual glands are misdirected through the greater superficial petrosal nerve to the lacrimal gland. This results in parasympathetic innervation of the lacrimal gland as well as the normal target, the salivary glands.

REFERENCES 1. Vidic B. The anatomy and development of the facial nerve. Ear Nose Throat J. 1978;57(6):236-42.

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2. Gasser RF, May M. Embryonic development of the facial nerve. M M, editor. New York: Thieme Straton; 1987. 3. Vidic B, Wozniak W. The communicating branch of the facial nerve to the lesser petrosal nerve in human fetuses and newborns. Arch Anat Histol Embryol. 1969;52:369-70. 4. Gasser R. The development of the facial nerve in man. Ann Otol Rhinol Laryngol. 1967;76:37-56. 5. Gassser, RF. The development of the facial nerve muscles in man. The American journal of anatomy. 1967;120:357-76. 6. Spector JG, Ge X. Ossification patterns of the tympanic facial canal in the human fetus and neonate. Laryngoscope. 1993;103(9):1052-65. 7. Nager GT, Proctor B. Anatomic variations and anomalies involving the facial canal. Otolaryngol Clin North Am. 1991;24(3):531-53. 8. Nager GT, Proctor B. The facial canal: normal anatomy, variations and anomalies. II. Anatomical variations and anomalies involving the facial canal. Ann Otol Rhinol Laryngol Suppl. 1982;97:45-61. 9. Antonelli PJ, Parell GJ, Becker GD, et al. Temporal bone pathology in scuba diving deaths. Otolaryngol Head Neck Surg. 1993;109(3 Pt 1):514-21. 10. Gasser RF. The early development of the parotid gland around the facial nerve and its branches in man. Anat Rec. 1970;167(1):63-77. 11. Gasser RF, Shigihara S, Shimada K. Three-dimensional development of the facial nerve path through the ear region in human embryos. Ann Otol Rhinol Laryngol. 1994; 103(5 Pt 1):395-403. 12. Waylonis GW, Johnson EW. Facial nerve conduction delay. Arch Phys Med Rehabil. 1964;45:539-47. 13. Crosby EC, Dejonge BR. Experimental and clinical studies of the central connections and central relations of the facial nerve. Ann Otol Rhinol Laryngol. 1963;72:735-55. 14. Radpour S. Organization of the facial nerve nucleus in the cat. In: Fisch U (ed.) Facial Nerve Surgery. Birminghan: Aesculapius Publishing; 1977. pp. 71-81. 15. Radpour S, Gacek RR. Facial nerve nucleus in the cat. Further study. Laryngoscope. 1980;90(4):685-92. 16. Radpour S, Gacek RR. Anatomic organization of the cat facial nerve. Otolaryngol Head Neck Surg. 1985;93(5): 591-6. 17. Nelson JR. Facial paralysis of central nervous system origin. Otolaryngol Clin North Am. 1974;7(2):411-24. 18. Jenny AB, Saper CB. Organization of the facial nucleus and corticofacial projection in the monkey: a reconsideration of the upper motor neuron facial palsy. Neurology. 1987;37(6):930-9. 19. Rhoton AL, Jr., Kobayashi S, Hollinshead WH. Nervus intermedius. J Neurosurg. 1968;29(6):609-18. 20. Silverstein H, Norrell H, Smouha EE. Retrosigmoid-internal auditory canal approach vs. retrolabyrinthine approach for vestibular neurectomy. Otolaryngol Head Neck Surg. 1987; 97(3):300-7. 21. McLaughlin MR, Jannetta PJ, Clyde BL, et al. Microvascular decompression of cranial nerves: lessons learned after 4400 operations. J Neurosurg. 1999;90(1):1-8.

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22. Redleaf MI, Blough RR. Distance from the labyrinthine portion of the facial nerve to the basal turn of the cochlea. Temporal bone histopathologic study. Ann Otol Rhinol Laryngol. 1996;105(4):323-6. 23. Fisch U, Esslen E. Total intratemporal exposure of the facial nerve. Pathologic findings in Bell’s palsy. Arch Otolaryngol. 1972;95(4):335-41.

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24. Baxter A. Dehiscence of the Fallopian canal. An anatomical study. J Laryngol Otol. 1971;85(6):587-94. 25. Fowler EP, Jr. Variations in the temporal bone course of the facial nerve. Laryngoscope. 1961;71:937-46. 26. Sunderland S. Anatomical features of nerve trunks in relation to nerve injury and nerve repair. Clin Neurosurg. 1970; 17:38-62.

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CHAPTER Facial Nerve Testing

37

Sachin Gupta, Brandon Isaacson

FACIAL NERVE DEVELOPMENT AND ANATOMY The facial nerve is a complex nerve composed of motor, sensory, and parasympathetic fibers that develop at 3 weeks of gestation. Complete separation of the facial and acoustic nerves occurs at 5–6 weeks, at which time the nervus intermedius also develops. At 8 weeks, the fallopian canal begins to develop and by the 16th week, the neural connections are completely developed. The fallopian canal continues to develop after the 16th week until birth, enclosing the facial nerve in bone throughout its course except at the facial hiatus in the floor of the middle cranial fossa.1 Dehiscence of the fallopian canal is most commonly seen adjacent to the oval window, at a reported rate of 25–55%.2 At birth, the facial nerve’s anatomy is similar to that of an adult, except in the region of the stylomastoid foramen. This area continues to develop after birth as the mastoid tip develops. Motor fibers originate from cell bodies located in the precentral and postcentral gyri of the frontal motor cortex. These fibers travel in the posterior limb of the internal capsule inferiorly to the caudal pons. There, the motor fibers supplying the facial musculature beneath the brows cross the midline to reach the contralateral motor nucleus in the reticular formation of the lower pons anterior to the fourth ventricle. The majority of motor fibers that supply the musculature of the forehead also cross the midline; however, a few fibers do not, instead traversing in the ipsilateral motor nucleus. Thus, muscles of the forehead receive innervation from both sides of the motor cortex, and so foreheadsparing facial paralysis raises suspicion of a central etiology.

Ch-37.indd 627

The motor fibers then pass dorsally, loop in a medialto-lateral manner around the abducens nucleus, and create a bulge in the floor of the fourth ventricle (the facial colliculus). This loop of the facial nerve forms the internal genu of the facial nerve.3-4 The nervus intermedius contains sensory, special sensory, and parasympathetic fibers. The nervus intermedius provides sensation to the posterior concha and external auditory canal. The nervus intermedius special sensory fibers supply taste sensation to the anterior two-thirds of the tongue. Afferent sensory fibers synapse with cell bodies in the geniculate ganglion at the first genu of the facial nerve. These sensory afferents then join the parasympathetic fibers, passing via the nervus intermedius to the nucleus tractus solitarius in the medulla. The parasympathetic portion of the nervus intermedius originates in the superior salivatory nucleus in the dorsal pons and innervates the lacrimal, submandibular, sublingual, and minor salivary glands. Both the motor root of the facial nerve and the nervus intermedius leave the brainstem near the dorsal pons at the pontomedullary junction (the cisternal segment of the facial nerve). Within the cerebellopontine angle (CPA), the nerve travels anterolaterally into the porus acusticus of the internal auditory canal (IAC), anterior to the vesti­ bulocochlear nerve. The cisternal segment is typically 24 mm in length.5 The nervus intermedius either integrates with the facial nerve as they emerge from the brainstem or joins near the meatus of the IAC.6 The facial nerve runs in the anterosuperior quadrant of the IAC. This intracanali­ cular segment of the facial nerve is approximately 8 mm in length. At the lateral end of the meatus, a horizontal

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segment of bone (the transverse or falciform crest) separates the facial nerve from the cochlear nerve that lies inferi­orly. Vertically, a segment of bone (Bill’s bar) separates the facial nerve from the superior vestibular nerve (which lies posteriorly). The fallopian canal begins as the facial nerve exits the IAC at the fundus. The major blood supply for the facial nerve proximally within the canal is the superficial petrosal artery, a branch of the middle meningeal artery, while the stylomastoid artery supplies the fallopian canal distally.7-8 The fallopian canal has three segments: labyrinthine, tympanic, and mastoid. The labyrinthine segment runs from the fundus of the IAC to the geniculate ganglion. It is both the narrowest (2–3 years duration. In that case, only neuromuscular transfers or static reanimation options remain. Favored neuromus­ cular procedures include the two-stage gracilis muscle transfer powered by the CFNG,32,33 the single-stage gracilis muscle transfer powered by the masseter nerve5,6,28,34 or the single-stage latissimus dorsi muscle transfer powered by the contralateral facial nerve.35

TECHNIQUES Orbital Management The need for periocular management of patients with complete facial paralysis is universal. Complications of facial paralysis in the eye area with inability to close the eye may lead to exposure keratitis, corneal ulceration, and potential loss of vision. Eyelid weight implants, lower eyelid suspension, and brow lifting procedures should be considered for rehabilitation of this critical zone. Evalua­ tion for a Bell’s phenomenon will determine adequate cor­ neal protection in the setting of incomplete eye closure. At the very minimum, corneal protection includes the use of lubricating drops during the day and lubricating ointments at night. Patients should always be surveyed for corneal anesthesia, especially after skull base surgery. If the cornea is insensate, the patient has an even greater risk for significant corneal injury and may need more advanced ancillary procedures, including temporary or permanent tarsorrhaphy. Eyelid weight implantation is the mainstay in rehabi­ litation of the paralyzed eye. The use of traditional bulky gold weights has been replaced by thinner low profile gold and platinum implants. Studies have shown that tradi­ tional gold weights have nearly a 40% long-term compli­ cation rate, most commonly bulging and astigmatism.36

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Table 40.3: Considerations for neural treatment of permanent complete facial paralysis

Prox FN

Distal FN

Motor endplates

Neural Rx

Alternate Rx

Within 48 hours (before Wallerian degeneration)

Normal

Lesion

Normal

Earliest primary repair

Close observa­ tion for sponta­ neous recovery of distal branch injuries medial to line from late­ ral canthus to oral commissure

Acute

Day 3–14: ENoG > 95% axon loss versus normal side

Normal

Lesion

Normal

Consider early FN decompres­ sion

Observation

Resection of parotid neoplasm w/seg­ mental loss of FN

Acute

Oncologic reasons may limit use of greater auricular nerve

Normal

Lesion

Normal

Immediate inter­ position graft

Acoustic neuroma resection with FN lesion

6–12 months

Early repair associated with best outcome. Poor long-term prog­ nosis. Intraop factors may elude to likelihood of facial nerve recovery and early two-stage CFNG considered

Lesion

Normal Normal

Combined CFNG and/or masseter nerve substitution

Modified hypoglossal nerve substitu­ tion

Congenital-Mobius syndrome

Any age Bilateral facial nerve deficit requires alter­ nate cranial nerve substitution

Lesion

Lesion

Abnormal

Bilateral masse­ ter to gracilis Favored

Alternate neuromuscular transfer

Marginal mandibu­ lar branch

12 months

Consider lidocaine test to simulate contralateral DLI paresis

Normal

Lesion

Abnormal

>2 years

Anterior digastric pedi­ cle flap requires neuro­ muscular training

Normal

Lesion

Abnormal

Cross-facial graft Contralateral or direct neuroti­ DLI chemode­ zation nervation or contralateral Anterior digas­ DLI resection tric transfer ±

Injury

Timing

Special considerations

Facial nerve transection

Acute

FN paralysis w/ temporal bone fracture

Chronic facial paralysis

12–18 months

Masseter nerve substi­ tutions favored

CFNG Uncertain Lesion

Abnormal

Combined CFNG and/or masseter nerve substitution

Modified hypoglossal nerve substitu­ tion

Uncertain Lesion

Abnormal

Neuromuscular transfer

Static reanimation in poor surgical candidates

Combined buccal CFNG for spontaneous smile & masseter— lower division FN for power and prevention of mass movement Prolonged facial paralysis

>2 years

Pediatric: CFNG with gracilis favored Advanced age: masse­ ter with gracilis favored

(CFNG, cross-facial nerve graft; DLI, depressor labii inferioris; ENoG, electroneuronography; FN, facial nerve).

The extrusion rate of low profile gold weights at 5 years is approximately 10%.37 The shift in paradigm to thinner pro­ file implants highlights the importance of protecting the

cornea without occluding the visual axis. Platinum is less allergenic and more dense than gold, allowing for an even thinner implant of equal weight. Platinum in the shape

Chapter 40: Facial Nerve Reanimation of links allows better eyelid contouring with substantially lower complication rates and is emerging as the implant of choice.38,39,40 Lagophthalmos and tearing abnormalities are debili­ tating and intervention should not be delayed beyond 3 weeks for the possibility of spontaneous recovery. This is especially true given the ease of reversibility and qualityof-life improvement during the waiting period for return of function.3,41 In cases of early paresis of uncertain dura­ tion, the immediate use of hyaluronic acid gel eyelid injec­ tion in lieu of surgical weight implantation is valuable. The technique is beneficial in its efficacy for the treatment of temporary lagophthalmos, low complication rate with care­ful injection technique, and ease of reversibility with hyaluronidase.42,43 After placement of topical anesthetic, suborbicularis oculi injections are placed in the pretarsal space in a serial threading pattern following the same prin­ ciples of eyelid weight implantation. The volume required depends on the degree of lagophthalmos and ranges from 0.3 to 1.0  cc, with the average patient requiring 0.5  cc.42 Initial pretarsal injections may be started with 0.3 cc in the awake patient in the semifowler (reclining lounge chair) position. Serial injection may be titrated at increments of 0.05 to 0.1  cc as needed until the desired eye closure is reached without obstructing the visual axis. In cases of severe lagophthalmos, additional injections may be placed more superiorly in the prelevator aponeurosis space to achieve the desired endpoint.43 As with all facial injections, careful injection techniques are required to minimize the risk of complications. Aspirating and checking for hema­ togenous flashback prior to injection is important to pre­ vent inadvertent intravascular injection. Although the use of other fillers has been described,43 Restylane (Galderma Laboratories, Fort Worth, TX, USA) may be preferred for initial injection in the eye area because of its less hydro­ philic nature and cross-linking pattern that empirically allows for more rapid enzyme reversal in the event of complication or early return of function.

Eyelid Weight Implant Insertion The weight of the implant may be assessed with sizers pre­ operatively. Incrementally heavier weights may be taped to the upper eyelid and eyelid closure is then evaluated while the patient is in the upright position. The appropriate weight is selected based on the lightest weight that permits eyelid closure comfortably. Typically, 1-gram weights are used in females and 1.2-gram weights are used in males.

673

Eyelid weight implantation (Figs. 40.5A to E) can be performed under local anesthesia with the patient in the semi-Fowler position. The incision is approximately 1 cm favoring the medial two thirds of the supratarsal crease. The incision is made through the skin and orbicularis mus­ cle parallel to the orientation of its fibers. Suborbicularis dissection is extended directly over the tarsal plate creating a pocket just above the eyelash margin. The pocket should be dissected so that approximately two thirds of the weight is medial to the mid-pupillary line. The weight should rest on the tarsal plate with the inferior border no more than 2 to 3 mm above the upper lash line. Superiorly, the weight is fixated with partial thickness sutures through the tarsus using a 4-0 clear nylon suture. If contouring links are being used, three sutures are sufficient.38 If the pocket is precise, suture fixation of the weight to the tarsal plate inferiorly is not necessary. The orbicularis muscle and the skin are closed in layers using interrupted 6-0 plain or fast absorb­ ing suture. Conforming spring implants have been reported and described in the literature. Their use has fallen out of favor due to a high propensity for extrusion.44 Despite the appropriate utilization of a weighted implant, there is still a frequent need for ointment during sleep.

Tarsorrhaphy The tarsorrhaphy procedure (Figs. 40.6A to C) is recom­ mended for facial paralysis patients who fail more conser­ vative methods of corneal protection and for all patients without an intact corneal blink reflex due to trigeminal nerve deficits. The loss of corneal sensation leaves them extremely susceptible to keratitis, corneal abrasions, and serious orbital injury. Tarsorrhaphies may be temporary or permanent and/or reversible. The duration of efficacy for a temporary tarsorrhaphy is approximately 4 to 6 weeks. Soft #4 French red rubber catheters or vessel loops may be cut into 3–4 mm pieces and fashioned as bolsters to but­ tress the skin in temporary tarsorrhaphy procedures. After local injection, a series of three horizontal mattress sutures are performed using 5-0 Prolene. The sutures are equally positioned staying approximately 5-10 mm in from the medial and lateral canthus.45 Approximately 5-6 mm above the upper lid margin, a partial thickness suture is placed that exits through the gray line. This then enters the oppo­ site gray line of the lower lid, again exiting approximately 5-6 mm below the lower lid margin. The suture is then passed through the center of the trimmed #4 French red rubber catheter or pierced through a trimmed vessel loop

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Otology/Neurotology/Skull Base Surgery

A

C

B

D

E

Figs. 40.5A to E: Eyelid weight implantation with platinum links. (A) Incision should be made in the supratarsal crease, centered on the medial two thirds of the upper eyelid. (B and C) A precise suborbicularis pocket is dissected over the tarsus and conforming platinum links are positioned as close as possible to the lid margin. (D) Partial thickness permanent sutures are placed through the tarsus to stabilize the implant. (E) Layered closure of orbicularis muscle and skin with fast-absorbing sutures.

bolster and then passed back in reverse through the lower and upper eyelid and superior bolster completing the hori­zontal mattress stitch before it is tied down. A lateral tarsorrhaphy permits long-term corneal pro­ tection with less visual obstruction and is easily reversible. Performing a lateral tarsorrhaphy requires the formation of an intermarginal adhesion. A 7–10-mm incision is made along the gray line with a scalpel extending medially from the lateral canthal angle. Westcott scissors may then be used to sharply dissect the anterior skin muscle lamella from the anterior tarsus taking care not to disrupt the eye­ lash insertion. Next, a strip of epithelium from the tarsal side is cut along the margin. The procedure is repeated along the upper eyelid margin leaving the anterior surface of the upper and lower eyelid tarsus exposed. 6-0 Vicryl sutures are then placed in interrupted fashion and tied. Finally, the lash bearing skin margins are allowed to close over the approximated tarsal plates without additional skin sutures.46

Neurorrhaphy Tension-free primary reattachment of a transected nerve gives the best chance of recovery. Most frequently this is seen in trauma where there is no loss of nerve tissue. The goal of any neurorrhaphy is to unite perineurial fascicles to permit axonal regeneration. All would agree that the best results are seen with the earliest repairs.13,25 Controversy remains surrounding the best way to accomplish this. Options for primary repair include suture neurorrhaphy or utilization of fibrin glue for coaptation. Surgeons who prefer to suture only the epineurium argue that excessive suturing of the perineurium may compromise the axonal load.20 Surgeons who advocate suturing the perineurium argue that epineurial scar tissue and retraction of the fascicles within the outer sheath is one reason for failures of the epineurium only technique. If perineurial suture techniques are employed, the nerve is prepared by trimming back the epineurium until the

Chapter 40: Facial Nerve Reanimation

A

C fascicles protrude from the cut surface.47 Most would agree that the fewest number of sutures required to pre­ cisely coapt fascicles is preferred if suture techniques are employed.20 Nonsuture fibrin glue coaptation has gained recent popularity and studies demonstrate equally effective out­ comes.48 Although there seems to be no additional longterm benefit, proponents argue it is quicker and easier than microsurgical suture techniques, especially in the hands of inexperienced surgeons.49,50 Future developments involve synthetic nerve sheaths impregnated with neurotropic factors to assist in nerve regeneration and reduce fibrosis at the point of coaptation.51 From a practical perspective, and for the purposes of techniques reviewed in this chapter, the caliber of nerves is taken into consideration when selecting a suturing technique. For example, the facial nerve trunk proximal to the pes anserinus has more fascicles and is more ame­ nable to perineurial suturing. Conversely, peeling back the

675

B

Figs. 40.6A to C: Temporary tarsorrhaphy. (A) Partial thickness suture is passed through a bolster (4-mm cut strip of red rubber or vessel loop) 5 mm above the lid margin. (B) A horizontal mattress suture is passed through the upper and lower lid margin at the gray line and supported by upper and lower lid bolsters. (C) Three tarsorrhaphy sutures are evenly spaced, starting at least 5 mm from the medial and lateral canthi.

epineurium in a distal monofascicular buccal branch may not be advisable. Another favored approach is the oblique preparation of the nerve providing a greater sur­ face area for any mode of coaptation (Fig. 40.7).47

Interposition Grafting When tension-free primary repair is not possible, the next best option is interposition (cable) grafting. Cable graft­ ing uses an autogenous donor graft as a conduit to permit axonal regeneration to span the lost distance. Unlike pri­ mary coaptation, regenerating axons must span two lines of coaptation with cable grafting. Sensory nerves such as the greater auricular nerve and the sural nerve are the most frequently selected grafts because of the low morbidity associated with the loss of sensation at their respec­ tive donor sites.52 Alternative donor nerves less commonly used include the lateral femoral cutaneous nerve, the medial antebrachial cutaneous nerve, and the

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Otology/Neurotology/Skull Base Surgery

Fig. 40.7: Neurorrhaphy. Oblique preparation of the nerve provides greater surface area for coaptation.

ansa hypoglossi. In settings of nerve sacrifice for tumor resection, studies have shown that positive margins, peri­ neural invasion, and radiation are not a predictor of the success of regeneration.53,54 The greater auricular nerve is limited to 7–8 cm, whereas the sural nerve may provide up to 35–40  cm of donor graft.40 The length of the graft does not affect graft survival because revascularization occurs segmentally, rather than longitudinally from the adjacent wound bed.20,55 For this reason, grafts should be longer than the defect because ­ graft contraction can occur. Occasionally, use of the greater auricular nerve may be contraindicated for oncologic reasons. The greater auricular nerve (C2/C3) is a sensory branch from the cervical plexus. It emerges from Erb’s point at the junction of the upper and middle third of the posterior border of the sternocleidomastoid muscle. It traverses the muscle parallel and posterior to the external jugular vein. The three branches of the greater auricular nerve (mastoid, auricular, and facial) can be harvested to bridge mutiple distal facial nerve branches to the main trunk. Sensory loss to the mastoid, ear lobe, and angle of the mandible will result. The greater auricular nerve can be found under a perpendicular line bisecting a line drawn between the mastoid tip and the angle of the mandible (Fig. 40.8).20 The sural nerve arises between the two heads of the gastrocnemius muscle and descends with the lesser sap­ henous vein wrapping posterior to the lateral malleolus and deep to the lesser saphenous vein to branch onto the side of the foot (Fig. 40.9).20 On occasion, tracing the nerve

Fig. 40.8: Surgical anatomy of the greater auricular nerve (GAN). The GAN runs parallel and posterior to the external jugular vein over the sternocleidomastoid muscle (SCM), emerging from Erb’s point at the junction of the upper and middle third of the SCM. It also reliably courses superiorly along a line that is perpendicular and bisects the M&M line (a line drawn between the mastoid tip and the angle of the mandible).

may provide a useful communicating bifurcating or trifur­ cating terminal branch that provides additional terminal arborization for reconstructing more than one facial nerve branch. Harvesting techniques vary based on physician’s preference and comfort with the anatomy. The traditional longitudinal open approach will provide the greatest expo­ sure. Alternately, harvesting can be performed through a series of small stair step incisions.33 Others suggest using a nerve stripper through fewer small incisions or harvest­ ing the nerve endoscopically using approaches similar to vein harvesting for coronary artery bypass grafting.56 In all cases, a pneumatic tourniquet is important to minimize bleeding and the nerve graft should rest in balanced saline solution upon harvest. Sensory loss to the side of the foot will result and in most cases this extends to the outer sur­ face of the fifth toe.57

Mobilization of the Mastoid Segment On rare occasion, additional length to close a very small gap between facial nerve ends for tension-free coaptation may be required. Additional dissection to drill out and mobilize the mastoid segment of the facial nerve provides a limited length advantage of approximately 1  cm and disrupts the blood supply in the process. The risks associ­ ated with this approach may be warranted in select cases

Chapter 40: Facial Nerve Reanimation

Fig. 40.9: Surgical anatomy of the sural nerve. The sural nerve arises between the two heads of the gastrocnemius, descends with the lesser saphenous vein (LSV) and wraps around posterior to the lateral malleolus and deep to the LSV.

where primary end-to-end coaptation (one suture line) circumvents the need for a cable graft (two suture lines), and thereby may improve outcomes.20,54

Cranial Nerve Substitution A nerve substitution must be considered in facial nerve injuries where the proximal facial nerve is unavailable. This implies redirection of motor axons from the donor nerve into a viable distal facial nerve. It is generally believed that neural techniques may be employed for up to 2 years with reliable outcomes.33 The high likelihood of distal facial nerve fibrosis and partial facial muscle atrophy limits suc­ cess beyond this time regardless of technique.18 If neural procedures are considered without muscle transfer within the 2 to 3 year window, the slow rate of nerve regeneration at 1 mm/day 40,44 must be factored. In these patients cranial nerve substitutions that do not preclude the possibility of future neuromuscular transfers are preferred. The next issue is the selection of donor nerves (Table 40.4). This has largely been limited by proximity, axonal density, and iatrogenic donor site morbidity. The ipsilateral hypoglossal, spinal accessory, and phrenic nerves have historically been used to supply functional axons to the extratemporal facial nerve trunk. The spinal accessory— facial nerve substitution and phrenic–facial nerve substi­ tution have largely been abandoned because of their rela­ tive donor site morbidity and their unnatural relationship to facial kinetics.

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The hypoglossal–facial nerve substitution has long been used in dynamic facial reanimation because of its acceptable relationship to facial kinetics. Based on the hypoglossal nerve, learned elevation of the tongue in the mouth helps simulate a smile and some voluntary move­ ments of facial expression. These voluntary actions are countered with undesirable involuntary facial movements that become apparent during eating and talking. Moreover, the morbidity associated with hypoglossal nerve sacri­ fice should not be underestimated. Many patients with facial nerve paralysis already have difficulty with speech and mastication. Sacrifice of the hypoglossal nerve in this setting may worsen oral motor dysfunction and in many cases is debilitating. The majority of patients with hypo­ glossal nerve loss will complain of speech and swallowing disturbances that worsen over time.58 Although still useful in the surgeon’s armamentarium, most would agree that complete hypoglossal nerve sacrifice is not a first choice procedure in any patient4,59 and a relative contraindica­ tion in patients with other lower cranial nerve deficits or at high risk for future cranial nerve neuropathy associa­ ted with skull base and intracranial etiologies.3,58 Because of the complexity of facial reanimation and the need for alternatives, several modifications to the classical ap­proach have been successfully employed over the years (1) to minimize complete hypoglossal nerve sacrifice and tongue atrophy with split nerve and jump graft techniques and (2) to decrease mass movement of the face by coapta­ tion to the lower division of the facial nerve only. The experience with masseter nerve substitution in the reanimation of bilateral congenital facial palsy (Möbius syndrome) has expanded our appreciation of the utility of this donor nerve. From these studies, the trigeminal masseter nerve substitution has gained popularity as the first choice donor nerve in a variety of applications. Pro­ ponents highlight its well-matched axonal load, insignifi­ cant donor site morbidity, geographic proximity requiring a single line of coaptation and predictable results.3,6,29 The anatomic relationship between the masseter and facial nerves is more closely related than any other nonfacial cranial nerve substitute. Advocates suggest this adds to the relative ease of cortical adaptation. The initial experiences report rapid reinnervation with return of motion averaging 95% of patients.3,29 Proponents generally site a stronger contraction of the gracilis muscle permit­ ting greater excursion of the commissure when the mas­ seter nerve is selected.33,34 The  disadvantage is the smile created is powered by the fifth cranial nerve and requires rehabilitation for the patient to learn to make it appear more natural. Proponents of this procedure continue to show improved outcomes, including “effortless” or voli­ tional smile with minimal effort in up to 75% of patients though cortical adaptation after 12–18 months of biofeed­ back physical therapy and training.5,6,34 In the classic two-stage CFNG and gracilis muscle transfer (Fig. 40.17), the first stage follows a procedure similar to the CFNG previously described. In this stage the donor nerves are isolated and coapted to the sural nerve on the unparalyzed side. After this, the nerve graft is tun­ neled through an upper lip sublabial incision to the para­ lyzed side. Surgeons will ordinarily wait for Tinel’s sign to indicate nerve regeneration or wait approximately 9 to 12 months to ensure that the maximum number of axons are available before proceeding with the second-stage muscle transfer.54,74 During the second stage, a cervicofacial flap approach to the paralyzed side is elevated and the denervated nerve

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Otology/Neurotology/Skull Base Surgery muscular bulk. Additional bulk may be reduced by remov­ ing the adjacent buccal fat pad. After arterial and venous anastomosis to the common facial artery and vein, the obturator nerve is microsurgically sutured with 10-0 nylon to the recipient nerve graft of choice. Careful skin closure and judicious use of drains is important to avoid vascular pedicle compression. The use of the masseter nerve to power the gracilis free-flap transfer has the advantage of a single-stage sur­ gery. The dissection involves only the affected paralyzed side of the face, and there is minimal donor-site morbidity. The donor nerve is in close proximity to the ideal location for a muscle transplant and a single obturator to masseter nerve coaptation will permit return of function as early as 10 to 12 weeks after the procedure.29

Fig. 40.17: Cross-facial nerve graft (CFNG) and gracilis muscle transfer. A two-stage approach is commonly used. In the first stage, a CFNG is coapted to a donor nerve from the unparalyzed side and tunneled to the contralateral side to permit axonal regene­ ration through the graft. In the second stage, the gracilis muscle is transferred and the obturator nerve is coapted to the CFNG on the paralyzed side. The transplanted muscle is suspended on the zygomatic arch and inserted on the oral commissure.

branches and the donor sural nerve graft stump are identi­ fied. The biggest complication associated with secondstage CFNG is neuroma formation.13,20 This should be recognized and removed prior to nerve graft coaptation. The gracilis muscle lies between the adductor longus and magnus in the medial aspect of the thigh and can be harvested via a medial thigh incision. The neurovascu­ lar bundle is located approximately 8 to 10 cm distal to the origin of the gracilis muscle from the pubic tubercle. The emergence of the neurovascular bundle determines the midpoint of the flap and 50% to 60% of the muscle diameter is then harvested.84 Typically, the transplanted muscle is aligned at a 30° angle to the horizontal and may be adjusted to counterbalance the patient’s normal side. The muscle is inserted into the oral commissure in two limbs with a portion overlying the upper lip and the second portion overlying the lower lip. A third limb may be extended to the alar base and recreation of the nasolabial fold through subdermal suture techniques is performed. The flap is positioned in much the same way as a static sling where the transplanted muscle is inserted into the zygomatic arch and pretragal region. It is important to support the muscle along the inferior border of the zygo­ matic arch to avoid producing an unsightly bulge from the

Static Reanimation and Ancillary Procedures Over the past several decades, there has been a shift toward the restoration of dynamic function. However, simple static techniques are still important given the numerous shortcomings of dynamic reanimation. Many patients with facial paralysis are not candidates for neural rehabilitation and may benefit from static reanimation or ancillary procedures. Many more patients have multiple chronic sequelae that cannot be fully ameliorated from a single approach. Patients with incomplete paralysis, poor outcomes after reinnervation surgery and or aberrant regeneration represent the largest segment of facial paraly­ sis patients and their treatment should not be overlooked. It is important to classify the nature of chronic facial paralysis: flaccid, hyperkinetic, or synkinetic. A full zonal assessment of the face may reveal several areas where static and ancillary procedures are paramount to improve facial symmetry and improve orbital, nasal, and oral func­ tion. Brow ptosis, eyelid malposition, hemifacial atrophy and ptosis, hemifacial spasm, blepharospasm, cervical dystonia, and facial synkinesis are frequent sequelae of chronic facial paralysis and many palliative options exist for their management. It is also important to appreciate the compensatory effects of facial paralysis are equally significant on the unparalyzed side. The effort to maintain oral competence and speech or elevate the brow in a futile attempt to maintain vision result in hypercontraction of the normal side, with exaggerated asymmetry and fatigue. Studies have also shown that contralateral reorganiza­ tion after facial nerve paralysis may increase the hyper­ excitability of the contralateral facial nucleus, especially notable in overcompensation of the blink reflex.85

Chapter 40: Facial Nerve Reanimation

Fig. 40.18: Critical landmarks to assess facial asymmetry. A. Resting brow ptosis. B. Superior eyelid malposition. C. Inferior eyelid malposition. D. Nasal base ptosis. E. Upper lip ptosis. F. Oral commissure droop. G. Philtrum deviation.

Primary areas of asymmetry are evaluated focusing on the eyebrow, ocular region, midface, nasolabial folds, buccal region, philtrum, oral commissure and lower lip, and cervical platysma. Seven critical distances at rest adap­ ted from the FACE software program86 can be compared with the normal side and used to set goals for static facial reanimation (Fig. 40.18): (1) Resting brow ptosis, (2) supe­ rior eyelid malposition, (3) inferior eyelid malposition, (4) nasal base ptosis in the vertical Y-axis, (5) Mid-upper lip ptosis, (6) oral commissure malposition, (7) philtral devia­ tion from the midline along the X-axis. Brow ptosis may be treated by a direct or minimally invasive brow lift. Orbital restoration may require upper lid or ectropion repair. Mitek anchor suture techniques may be used to adjust the nasal valve, philtrum, and upper lip. Facial asymmetry may be balanced with fascia lata or Gore-Tex facial slings and facial rhytidecotmy. Faulty nerve regeneration may require treatment of syn­ kinesis or hyperkinetic facial spasms with chemodener­ vation, selective myectomy, selective neurolysis, and biofeedback exercises.

Chronic Orbital Sequelae There should also be an appreciation of how facial tone (flaccidity versus hypertonic spastic contracture) and syn­ kinesis affect the eye area. The most frequent manifestations of facial synkinesis are an abnormal blink reflex and eye closure with mastication, speech or smiling or conver­sely

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twitching of the corner of the mouth with each blink. Hypertonic contraction will manifest as excessive wrin­ kling and narrowing of the orbital palpebral fissure in addi­tion to prominent bulging of the cheek with a deep­ ened nasolabial fold, loss of lip depressor function, and chin dimpling. This is in contrast to flaccid paralysis where there is effacement of wrinkles, eyebrow droop, and palpe­ bral fissure enlargement, in addition to nasal deviation to the unparalyzed side or flattening of the nasal ala, lip mus­ cle atrophy, flattening of the nasolabial fold, droop of the oral commissure, and dynamic deviation of the lips and philtrum. Long-term flaccid paralysis may lead to signifi­ cant brow ptosis and paralytic eyelid ectropion requiring static ancillary procedures. Facial synkinesis and hyper­ tonic spastic muscle contracture are commonly seen after faulty facial nerve regeneration. Although appropriate use of physical therapy has proven helpful, there is still a con­ cern that inappropriate use of electrical stimulation may aggravate synkinesis and hypertonicity.10 Physical therapy in the form of reproducible mirror exercises and biofeed­ back for muscle relaxation and stimulation remains advo­ cated.27,82 This is often used in conjunction with surgery and botulinum toxin chemodenervation87,88 and will be reviewed later in this chapter.

Asymmetric Brow Ptosis Repair Brow ptosis is commonly seen after frontal branch facial nerve paralysis. This may result in pseudoblepharopto­ sis due to heaviness of the brow skin. Several procedures are available for the correction of brow ptosis. The patient must be evaluated in the upright position manually elevat­ ing the brow to the desired position. Any difficulty with eye closure in the corrected position should be noted, especially if the patient has no return of function. The direct brow lift allows some shaping of the brow contour and gives significant brow elevation, which is often neces­ sary for patients suffering from facial paralysis.89 One dis­ advantage of the direct brow lift is the scar along the upper border of the brow. Careful incision, meticulous layered closure, and inversion of the wound edges using vertical mattress sutures will result in an acceptable scar outcome in most patients. Alternate methods have successfully employed minimally invasive suspension techniques90 for the selective contouring of brows in both the paralyzed and unparalyzed brow.

Direct Brow Lift With a direct brow elevation procedure (Figs. 40.19A to F), a fusi­form crescent-shaped incision is drawn along the brow margin based upon the width of skin to be removed as

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Figs. 40.19A to F: Direct brow lift. (A) Incision planning for medial/middle brow ptosis. (B) Incision planning for lateral brow ptosis. (C) The blade is beveled parallel to the growth of the brow hair follicles. (D) The skin flap is elevated in the subcutaneous plane. (E) The frontalis is suture fixated to the periosteum in the desired position. (F) Meticulous muscle and skin-layered closure.

determined preoperatively. The extent and shape of excision is determined by the pattern of brow ptosis.

The supraorbital neurovascular bundle is injected with local anesthetic as it exits the supraorbital notch. Local

Chapter 40: Facial Nerve Reanimation anesthetic is injected along the skin incision lines. The inferior incision is made orienting the blade parallel to the direction of the hair follicles. Next, the superior incision is made parallel to the bevel used along the inferior incision to permit appropriate wound closure. The skin flap is dissec­ ted in the supra-SMAS subcutaneous plane above the fron­ talis muscle, taking care to remain very superficial in the region of the supraorbital nerve. In the setting of facial paralysis the brow can be suture fixated through the front­ alis muscle to the frontal bone periosteum with two to three 4-0 clear nylon sutures to support the repair and shape the arch as desired. The subdermal layer is closed with 5-0 Vicryl sutures. Interrupted vertical mattress sutures are then placed with 5-0 Prolene, carefully everting the wound margin. Antibiotic ointment and a compression dressing are then placed.91

Minimally Invasive Brow Suspension One of the most obvious sequelae of facial paralysis is the involuntary disgusted or angry appearance associated with facial asymmetry and contralateral overcompensation. Selective brow suspension as described by Costantino et al.90 is a very powerful technique that gives the surgeon complete control over brow contouring on both the para­ lyzed and unparalyzed sides (Figs. 40.20A to C). Selective suture placement and cinching can be applied like mari­ onette strings to elevate and reshape the brows into a more gentle aesthetic arch. Further the tremendous control in

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elevation allows for conservative upper lid skin excision as needed to optimize aesthetics without compromising eye closure (Figs. 40.21A to F). In this procedure, three oblique 0.7-mm brow inci­ sions are demarcated parallel to the orientation of the hair follicles in the eyebrow. The degree of medial, central, and lateral brow suspension desired and thus the ideal place­ ment of the incisions are assessed preoperatively. Care is taken to survey where brow elevation elevates the critical areas of ptosis, without further compromising eye closure. An additional three 1.5-cm incisions are marked approxi­ mately 1 cm above the hairline in the desired vector of pull just above the areas where brow elevation is desired. Most commonly, the first vertical scalp incision is made approxi­ mately 1.5-cm paramedian, the next is made between the midpoint of the brow and the desired arch point and a third incision is made at or below the lateral temporal fusion line and oriented obliquely (perpendicular to the lateral brow). Dissection is then performed in the subperiosteal plane undermining the soft tissue from the central cal­ varium and frontal bone around each of the medial inci­ sions. Elevation is continued anteriorly to the supraorbital rim avoiding the region of the supraorbital neurovascular bundle. The use of an endoscope is not required in cases of permanent frontal nerve paralysis as long as the dissection remains mindful of the position of the supraorbital notch and its anatomic relevance. The retaining ligament along the superior orbital rim is released with the dissector until

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Figs. 40.20A to C: Minimally invasive brow suspension. (A) Subperiosteal elevation is performed until the arcus marginalis is released superiorly. (B) 4-0 clear nylon brow suspension sutures are tunneled out the scalp incisions using a Hewson suture passer. (C) Three suspension sutures are tightened to permit selective brow contouring.

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Figs. 40.21A to F: Static reanimation in patient with right partial facial paralysis. Midface Mitek anchor suspension, minimally invasive browlift, and conservative blepharoplasty were performed. Chemodenervation was not used. (A,B,C: preoperative views; D,E,F: postoperative views). (A) Left compensation to improve right pseudoblepharoptosis leaves patient with an involuntary angry appearance. (B and C) Note flaccid nature of partial paralysis on open-mouth smile with limited show of right maxillary teeth. (D) Note selective treatment of medial and middle brow to permit brow reshaping bilaterally. Conservative upper lid skin excision without compromise of eye closure. Improved oral commissure position at rest. (E) Improved position of the philtrum and right upper teeth show. (F) Three-quarters view.

the brow is fully released. The lateral dissection is continued through the lateral temporal incisions to elevate the super­ficial temporal fascia from the deep fascia and then medially break through the temporal fusion line to join the subperiosteal space over the frontal bone. Brow incisions are then made through the skin and subcutaneous tissue beveling the blade parallel to the hair follicle. The skin and subcutaneous fat are undermined from the underlying frontalis muscle and fascia for a few millimeters on each

side of the incision. A Hewson suture passer is then passed from the scalp incision and used to perforate the frontalis muscle as it exits the brow incision. A generous horizontally based suture is then passed through the frontalis muscle and fascia in this area and brought back out through the scalp incisions with the assistance of the suture passer. Care is taken to avoid catchment of subcutaneous tissue in this stitch to prevent brow puckering. A small amount of puckering may be treated with additional subcutaneous

Chapter 40: Facial Nerve Reanimation release through the brow incision. Caution must be taken to avoid cutting the suture or compromising the suspen­ sion by violating the muscle during this maneuver. Each of three sutures is placed in the desired position and simi­ larly brought out through the scalp incisions. Sequential suture stabilization to the galea aponeurosis is performed tying the suture down to the desired position with approxi­ mately 20% overcorrection. Once the sutures are tightened sufficiently, the scalp incisions are closed in a single layer with staples and the brow incisions are closed in a single layer with 6-0 Prolene. Antibiotic ointment is applied to the incisions and a turban pressure dressing is applied for 48 hours.

Ectropion Repair In ectropion, the eyelid margin is everted away from the globe. This exacerbates inadequate corneal protec­ tion and results in dysfunctional tear drainage from poor apposition of the puncta to the globe. In facial paralysis over time, the progressive loss of eyelid tone and muscle atrophy exacerbates this laxity. The most useful eyelid shortening procedures include the lateral tarsal strip can­ thoplasty and a simple wedge resection with or without orbicularis tightening. In paralytic ectropion, the hypo­ tonic orbicularis oculi muscle results in the outward dis­ placement of the lower lid. Over time, the gravitational downward traction of the droopy cheek complicates the condition. The canthal ligaments are usually normal. The goals of management of paralytic ectropion are corneal protection and restoration of normal tear drainage and symmetry. A mild ectropion may respond to a simple late­ ral canthopexy that shortens the interpalpebral fissure and helps reoppose the lid margin. In more severe cases, width shortening procedures may be required but often must be combined with cheek suspension to alleviate the progressive downward traction associated with midface ptosis.

Lateral Tarsal Strip Fixation and Canthoplasty for Eyelid Shortening The lateral tarsal strip procedure (Figs. 40.22A to F) is used in cases where lower lid laxity will benefit from eyelid shorten­ ing. Once the lateral canthal tendon is transected laterally, the anterior and posterior lamella of the lateral canthal tendon are removed, leaving a strip that can be shortened to the desired length and reattached. The initial incision is made from the lateral canthus extending out 1 cm laterally.

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The dissection is carried down through the orbicularis muscle until the orbital septum is identified. Suborbicu­ laris dissection of the anterior lamella is performed over this layer until the arcus marginalis is identified. The eye­ lid is retra­cted medially and a lateral canthotomy is made down to the orbital rim transecting and releasing the infe­ rior limb of the lateral canthal ligament. The anterior skin muscle lamella is then separated from the tarsal margin along the gray line for a distance of 5 to 10 mm depending on the amount of lid shortening required. Next, the retrac­ tors and conjunctiva are cut along the inferior border of the tarsus beneath the split section. This may necessitate some cauterization of the palpebral vessels. A strip of epithelium is then excised from the dissected portion of tarsus. The conjunctival epithelium along the posterior surface of the tarsus is then scraped with a scalpel blade. The dissected tarsus is then cut to the desired length leaving a terminal strip approximately 3-4 mm wide and 4 mm long. Using a 4-0 Mersilene or 4-0 Vicryl suture on a small half circle needle, the strip is fixated through the periosteum at Whitnall’s tubercle along the medial aspect of the lateral orbital rim. This repositions the lower lid back in apposi­ tion with the globe. The skin muscle flap is then draped laterally. The excess skin is examined and a small triangu­ lar flap is excised. The canthal angle is then reconstructed with a 6-0 Vicryl suture and the orbicularis oculi muscle and skin are closed in layers with interrupted 6-0 fast absorbing plain gut suture. Caution must be taken to avoid overshortening, resulting in a bow-string effect that worsens scleral show. There is also a high propensity for overelevation of the canthal angle, which may not be apparent in the supine position. Postoperatively, some stretching will occur within the first 2 weeks.92

Lower Eyelid Spacer Graft Significant laxity and lower lid retraction may not be resolved with eyelid shortening procedures. Spacer grafting to the intermediate or posterior lamella may be required to support and elevate the lower lid position. Cadeveric banked sclera, hard palate mucosa or carti­ lage spacer grafts have been described.93 In the setting of paralytic ectropion, the heaviness of midface ptosis and the loss of orbicularis oculi strength substantially weak­ ens the lower lid. In these cases, there is no cicatricial loss of skin in the anterior lamella, nor loss of conjunctiva in the poste­rior lamella. The use of a semicircular convex graft derived from cadaveric banked sclera may be placed through a subciliary or transconjunctival approach in the

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Figs. 40.22A to F: Lateral tarsal strip fixation and canthoplasty. (A) 1-cm incision is made extending laterally from the lateral canthus and suborbicularis dissection is performed until the arcus marginalis is reached. (B) Lateral canthotomy is performed and the anterior and posterior lamella of the tarsus are removed along the desired length. (C) The dissected tarsus is then cut to the desired length leaving a 4 x 4 mm terminal strip. (D) The strip is than fixated to the periosteum at Whitnall’s tubercle to reoppose the lower lid to the globe. (E) Skin muscle flap is redraped and conservative triangle flap of excess is excised. (F) Layered closure is performed.

Chapter 40: Facial Nerve Reanimation

Fig. 40.23: Cadeveric banked sclera used as a lower lid spacer graft in paralytic ectropion repair. Black arrow: scleral graft; white arrow: orbicularis oculi muscle.

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Fig. 40.24: Paralytic nasal valve collapse. Note the downward shift in the left nasal side wall and ala.

suborbicularis plane (Fig. 40.23). The graft is then secured to the periosteum at the level of the arcus marginalis to support the lower lid complex. This procedure can be performed in conjunction with lateral canthal tightening procedures and/or midface suspension to support the repair and prevent recurrence.93

Mitek Anchor Suspension for Nasal Valve and Philtrum Adjustment The effect of paralysis on the nasal airway is frequently neglected. The dominant nonparalyzed side imposes severe deviation of the philtrum and subnasal region (Fig. 40.24). Combined with the progression of midface ptosis and weakening of the nasalis muscles, profound external and internal nasal valve compromise results. Treatment of the alar base with fascia lata slings33 or Mitek anchor suture techniques94 have demonstrated good out­ comes. Alternative approaches include the use of classic alar batten grafts to stiffen the nasal sidewall. In addition to nasal valve repositioning, upper lip asymmetry can effectively be treated by a modified sub­ nasal lift that employs the 2.0 mini-Mitek bone anchor system (Dupuy Mitek, Raynham, MA, USA) for soft tissue stabilization (Figs. 40.25A to C).94 A circum-alar incision is made that may include excision of a crescent-shaped strip of skin as in a subnasal labial lift (Figs. 40.26A to D). The upper skin incision is then taken down and the soft tissue is elevated in the subperiosteal plane. A mini-Mitek anchor custom drill bit is used to drill a hole in the maxilla adjacent to the piriform aperture. The bone anchor is then firmly

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Figs. 40.25A to C: Mitek bone anchor for midface suspension. (A) Drill hole with Mitek custom drill bit. (B) Insert Mitek firmly into predrilled hole. Pull back on the applicator to release sutures and deploy anchor. Remove inserter. (C) Deployed Mitek minianchor fixated to bone with two free suture limbs available for soft tissue repositioning.

inser­ted into the predrilled hole. The applicator is retracted to release the sutures and deploy the anchor. The two free suture limbs may then be used to reposition the soft tis­ sues. Success with maneuvering soft tissue must not rely solely on the strength of the suture but also in the tech­ nique used to plicate or advance the underlying muscula­ ture into the desired position. The vector advantage of pull corresponds to the position of anchor placement. Place­ ment at the level of the piriform aperture is reliable to treat the external nasal valve and alar tissue, permit eversion of

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Figs. 40.26A to D: Subnasal lift with Mitek anchor suspension. (A) Preoperative: deviation of philtrum, left upper lip malposition, and elongation. (B) Postoperative: note correction of philtrum position and angle, lip shortening in the X-axis and lip elevation and eversion in the Y-axis. (C) Upper lip circum-alar approach and skin excision. (D) Closure allows for adjustment of nasal ala and philtrum.

the upper lip, and to a lesser degree improve philtral and lateral oral commissure position.94 After bone stabilization of the Mitek minianchor, one suture arm is passed through the midpoint of the upper lip segment to evert the upper lip and elevate the oral commissure. The second suture limb may then be used to elevate and lateralize the alar base and reposition the philtrum. Moderate overcorrec­ tion is recommended because relaxation always occurs.

Lower Facial Suspension and Static Slings In end-stage cases where the goal is not production of a spontaneous smile, many static reanimation techniques have been successfully employed. Tensor fascia lata or Gore-Tex (W.L. Gore & Associates, Inc., Flagstaff, AZ, USA) reliably provides material to support static facial suspen­ sion and improve symmetry at rest. The goal of static tech­ niques is to restore the effacement of the nasolabial fold and the loss of facial domain seen with severe midface and lower face ptosis. An open rhytidectomy approach may be utilized to place slings fashioned into independent slips. The slips are connected to the orbicularis muscle in the

area of the oral commissure at the upper and lower lip and suspended to the zygomatic arch to elevate the corner of the mouth at a position slightly higher and more lateral than the resting contralateral unparalyzed side. Overcor­ rection is required because relaxation always occurs. Gore‑Tex alloplastic material has been shown to decrease the risk of attenuation, more commonly seen with fascia lata. But as an alloplastic implant it does carry a greater risk of infection and inflammation.59 Alternately, Alam95 describes the use of a minimally invasive percutaneous sling that addresses recreation of the nasolabial fold and oral commissure suspension with a much smaller Gore-Tex implant (Figs. 40.27A to D). In this technique, a stab incision is made in the superior nasola­ bial fold at the level of the piriform aperture. A second stab incision is made at the inferior nasolabial fold at the level of the oral commissure. A harvesting liposuction cannula is used to dissect a tunnel releasing the nasolabial attach­ ments. A thin strip of Gore-Tex (4 cm x 5 mm) is then sutured to the cannula and tunneled out the opposite end. Next, a temporal incision is made and taken down to the level

Chapter 40: Facial Nerve Reanimation

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Figs. 40.27A to D: Minimally invasive percutaneous facial sling. (A) A liposuction cannula is tunneled below the nasolabial fold and used to guide a thin strip of Gore-Tex. (B) Each suspension suture is guided on a long Keith needle through the scalp incision. This is then passed through the Gore-Tex and skin and percutaneously reversed back out the scalp incision. (C) Four to five suspension sutures are tied down to the deep temporalis fascia at the desired level of correction. (D) The Gore-Tex implant is trimmed and the incisions are closed.

of the deep temporalis fascia. 4-0 clear nylon or Prolene suture is threaded on a 4 inch abdominal Keith needle and passed from the temporal incision through the implant and passed percutaneously through the nasolabial fold. The pass is reversed taking another bite through the implant and exiting back through the temporal incision. Four to five suspension sutures approximately 7  mm apart are placed along the length of the strip. The sutures are passed through the deep temporal fascia and secured at the desired position. Once stabilized, the ends of the

Gore-Tex anchor are trimmed, the facial incisions are closed with 4-0 nylon and the scalp incisions are closed with staples. Antibiotic ointment and a sterile turban pres­ sure dressing are applied.

ABERRANT FACIAL NERVE REGENERATION Facial synkinesis is the most common sequelae of neurotme­ sis and its debilitating nature should not be underestimated.88

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It is important to characterize the recovery of meaningful function in facial paralysis patients. Hyperkinesis and syn­ kinesis often masquerade as return of facial function, but they are still a form of debilitating paralysis.96 The chronic spasm of hyperkinetic paralysis and the uncoordinated movement of synkinetic paralysis, often confound the uncontrolled and weak return of voluntary movement in recovering patients. During the normal course of axonal regeneration each parent axon gives rise to up to 25 donor axons.58 Denerva­ ted muscles produce a stimulus to encourage this axonal spreading. Many of these regenerating axons fail to make a connection with their peripheral target and are lost, whereas others reach incorrect end targets (see Figs. 40.4A a to C). The pathogenesis of synkinesis and abnormal mass movement results from a single motor neuron acti­ vating antagonistic or separate muscle groups. This “poly­ innervation” is a maladaptation that results in synchronous activation of diffe­rent motor endplates by uncoordinated motor neurons.58 In addition to axonal misrouting at the site of the lesion, the resulting lack of neuronal input leads to hypersensitivity of the pontine nucleus proximal to the lesion and Wallerian degeneration distal to the lesion. With this as the prevailing theory, more proximal lesions

are associated with greater nerve damage and a higher incidence and severity of synkinesis and abnormal facial movement.88 Modern-day rehabilitation of permanent facial paralysis is best performed through multimodality treatment includ­ ing surgical intervention, biofeedback physical therapy, and chemodenervation to treat chronic sequelae. In seve­rely debilitating cases of synkinesis, cross-facial nerve graft­ ing has been successfully employed in conjunction with chemo­denervation and muscular retraining to override the faulty pathways and re-establish coordinated facial movements based on the unparalyzed side.88 The com­ monplace utility of this is still under investigation.

Anatomy of the Facial Muscles The workhorse muscles of the face are (1) the orbicularis oculi, which forms a sphincter to close the eyelids, (2) the orbicularis oris, which forms a sphincter around the opening of the mouth, and (3) the buccinator, which forms the fleshy part of the cheek. It is important to understand the relationship of muscles especially when attempting to treat disturbances such as facial synkinesis and myofascial spastic facial contracture (Fig. 40.28). The fibers of the buc­ cinator run horizontally from the deeper muscular layer

Fig. 40.28: Mimetic muscles that animate the lips. In addition to the sphincter action of the orbicularis oris muscle (green arrows), several muscles act in concert to animate the lips. The right side of the diagram (blue arrows) demonstrates the vector of pull of each of the superficial muscles. These muscles are innervated by the facial nerve branches entering from their deep surface. The left side of the diagram (red arrows) demonstrates the vector of pull of each of the deep muscles. These three muscles are innervated by the facial nerve branches entering from their superficial surface.

Chapter 40: Facial Nerve Reanimation

Fig. 40.29: Anatomy of the facial muscles.

toward the angle of the mouth. It additionally gives fibers to the orbicularis oris making these muscles intimately related. The buccinator muscle is required to whistle and more importantly press the cheek against the gums to prevent the escape of food into the vestibule of the mouth during mastication. In cases of buccinator paralysis, par­ tially masticated food or saliva accumulates between the cheeks and the gums and may cause drooling from the corner of the mouth. The mimetic muscles of the face (Fig. 40.29) work in concert to produce endless variations in facial expression. By definition, these muscles have a bony origin, reside within a superficial fascia, and unlike other muscles they insert only into the skin of the face and lack tendons.14 The frontalis, procerus, and corrugator supercilii muscles comprise the brow elevators and depressors. The com­ pressor and dilator naris comprise the nasalis muscula­ ture. The levator labii superioris, levator labii superioris alaeque nasi, the zygomaticus major and minor muscles, the levator anguli oris, the depressor anguli oris (DAO), the depressor labii inferioris (DLI), mentalis, and risorius muscles are among the many small muscles innervated by the lower division of the facial nerve. The cervical branch of the facial nerve innervates the platysma muscle.

Facial Synkinesis Facial synkinesis is one of the most important issues affecting recovery of facial nerve function. Facial synkine­ sis may occur after any form of injury to the facial nerve and

697

full transection of the nerve is not required. Facial synkine­ sis is commonly seen as a sequelae of Bell’s palsy where edema leading to ischemic neurotemesis is the cause. Abnormal movements are usually noted 3 to 4 months after the time of injury due to axonal sprouting but may be seen as early as 6 weeks after facial nerve injury with early failure of pontine synaptic inhibition13 Facial synki­ nesis may continue to progress or worsen in parallel with regeneration for two years or more.4,58 An uncontrolled disgusted facial grimace is often seen with hypertonic contraction of the nasolabial fold and the patient commonly complains of severe muscle pain and tension in the zygomaticobuccal distribution. Abnormal tonic spasms may also involve narrowing of the palpebral aperture from the orbicularis oculi, popply dimpling of the chin from the mentalis and cervical spasm from the platysma. Over and above this hemifacial spasms com­ monly exhibit involuntary muscle twitching. EMG find­ ings are pathognomonic for this condition. EMG will commonly reveal synchronized activity of the motor unit of the involved facial muscles. In contrast to a normal maxi­mal firing rate of 50/s, classical hemifacial spasm muscles will reflect a firing rate of up to 350/s.18

Botulinum Toxin for Selective Chemodenervation and Ancillary Procedures Botulinum A toxin has proven an effective temporary treatment for the control of aberrant facial kinetics such as blepharospasm, hemifacial spasm, and facial synkine­ sis, atonic spasm following faulty regeneration and other dystonic disorders. Chemodenervation with botulinum toxin inhibits the presynaptic release of acetylcholine at the neuromuscular junction. The process of chemodener­ vation with botulinum toxin produces a paralytic effect that is dose related. Dosages and injection sites must be carefully mapped for each individual patient. Botox (Aller­ gan, Inc., Irvine, CA, USA) and Dysport (Galderma Labo­ ratories, Fort Worth, TX, USA) are popular alternatives. It is important to appreciate that the dosage units are not interchangeable. On average, clinicians accept the con­ version ratio of 3 units Dyport (abobotulinum toxin A) to 1 unit Botox (onabotulinum toxin A), and modify the dosages accordingly.97 To make this easier, a 300-unit vial of Dysport is roughly equivalent to a 100-unit vial of Botox. For the purposes of this chapter, recommended units will be expressed as Botox units. Table 40.5 explains the

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Otology/Neurotology/Skull Base Surgery

Table 40.5: Facial muscles, action, and therapeutic implications for chemodenervation*

Paretic muscle Botox† —

Normal muscle Botox† 3–6 unit

Facial nerve Frontal

Muscle Procerus

Frontal

—

3–6 unit

Frontal

Corrugator supercilii Frontalis

—

8–12 unit

Frontal & zygomatic

Orbicularis oculi

6–8 unit‡

6–8 unit

Zygomatic & Buccal

Zygomaticus major

1–2 unit‡

1–2 unit‡

Buccal

Zygomaticus minor

1 unit‡

1 unit‡

Buccal

Levator labii superioris Levator labii supe­ rioris alaeque nasi

1–2 unit‡

1–2 unit‡

1 unit

1 unit‡

Buccal

Risorius

—

3 unit

Buccal

Buccinator

1–2 unit

—

Buccal

Levator anguli oris

—

—

Buccal

Orbicularis oris

—

—

Buccal Buccal Marginal mandibular

— — 2–3 unit

— — 2–3 unit

—

2–4 unit

Marginal mandibular

Dilator naris Compressor naris Depressor anguli oris Depressor labii inferioris Mentalis

3 unit

3 unit

Cervical

Platysma

8–10 unit per band

8–10 unit per band

Buccal

Marginal mandibular

Action Common finding Pulls medial brow down Contralateral hypertonic Pulls medial brow Contralateral down and in hypertonic Elevates brow Contralateral for symmetry Closes eyelid, Synkinesis blink, narrow depresses lateral brow palpebral fissure Elevates corner of Treat hypertonic/ upper lip balance smile Elevates upper lip Treat hypertonic Elevates upper lip & middle nasolabial fold Elevates medial nasolabial fold and nasal ala Lateral pull on corner of mouth Compresses cheek & lateral pull on corner of mouth Pulls corner of mouth up and medial Protrudes and puckers lips Flares nostrils Compresses nostrils Depresses corner of mouth Depresses lower lip

Upper lip retraction/ incisor show Alar flaring, philtrum deviation

Pulls chin upward and protrudes lower lip Depresses corner of the mouth

Chin dimpling

Balance smile Severe NLF spasm may be associated with buccinator hypertonicity Injection rarely indicated Injection rarely indicated Injection rarely indicated Injection rarely indicated Downturned commissure Contralateral only for symmetry

Downturned commissure, lip synkinesis

*Sample strategy for initial dosing of botulinum toxin during serial titration. † Only hypertonic or synkinetic target muscles are selected for treatment. ‡ High-risk areas for iatrogenic overdosing.

independent actions of each of the facial muscles and sample starting doses for therapeutic intervention. Fa­ cial diagrams should be used to document dosing, which can be titrated in serial visits 2–3 weeks apart until the appropriate therapeutic dosage is determined. Denerva­ tion persists on average 3 to 4 months, but the duration of action is patient specific depending on collateral sprouting to restore neurotransmitter release at the neuromuscular

junction. Prolonged repetitive treatment can produce muscle atrophy and in some cases lengthen the duration of action.98 Patients with hyperkinesis frequently exhibit nar­ rowing of the palpebral fissure that worsens with fatigue (Figs. 40.30A to F). This originates from orbicularis oculi spasm and may or may not be seen in tandem with oroocular blink synkinesis. In both scenarios, treatment of the

Chapter 40: Facial Nerve Reanimation

A

B

C

D

E

F

699

Figs. 40.30A to F: (A to C) Evaluation of patient with left hyperkinetic and synkinetic facial paralysis for serial Botox chemodenervation. (D to F) Follow-up evaluation of left hyperkinetic facial paralysis for serial dosing after first Botox chemodenervation. (A) At rest: note the hyperkinetic left zygomaticus muscles causing severe facial contracture at the nasolabial fold with left upward deviation of the upper lip complex. Normal depressor anguli oris (DAO) activation on the right is perceived as an oral commissure droop. Also note right overcompensation causing shift of the philtrum to the weaker left side. (B) Smile: note the hyperkinetic left orbicularis oculi causing narrowing of the palperbral fissure. The patient also suffers from left smile mediated oro-ocular blink synkinesis. Note the mentalis dimpling on the left and hyperkinetic left platysma muscles. The patient has generalized right over-compensation causing asymmetry in other views (not provided). (C) DOSE TITRATION 1: right frontalis/corrugator/procerus (15 u), bilateral orbicularis oculi (6 u each), left zygomaticus major (3 u), left zygomaticus minor (1 u), bilateral mentalis (3 u each), right DAO (3 u), right risorius (3 u), left platysma ( 6 u per band × 2). (D) At rest: note improved relaxation of hyperkinetic left zygomaticus muscles with improved upper lip and philtrum position. Right DAO relaxation provides oral commissure symmetry at rest. Orbicularis relaxation with lateral brow elevation at rest. (E) Smile: improved hyperkinetic left orbicularis oculi with incomplete widening of the palpebral fissure. Persistent mentalis dimpling on the left and persistent dominant hyperkinetic left platysma band. Persistent oro-ocular blink synkinesis with modest improvement. (F) DOSE TITRATION 2: left orbicularis oculi (6 u), left mentalis (3 u), left platysma (6 u).

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Otology/Neurotology/Skull Base Surgery

orbital orbicularis oculi (lateral crow’s feet) alone may be insufficient to correct the problem. The problem resides in the hyper­kinetic pretarsal and preseptal orbicularis, a zone not routinely treated in aesthetic applications. Can­ didates for this treatment should have a good snap test without laxity. Patients with oro-ocular synkinesis and hyperkinesis are treated cautiously in the preseptal orbi­ cularis oculi to minimize hyperactivity. Care is taken to start with low doses to prevent upper lid ptosis, ectropion, and untoward effects. It is also important to appreciate the antagonistic paired action of muscles when treating facial zones by chemo­denervation. Paralyzing one muscle group invari­ ably has some effect on its antagonistic pair. In facial para­ lysis, this may be a favorable outcome, but only when used intentionally. Pitfalls are seen with selective treatment of the procerus and corrugator brow depressors leading to rebound hyperactive furrows of the frontalis. Isolated treatment of the DAO may result in unopposed mentalis action with an unnatural upturned smirk. Treatment of the DAO and the mentalis muscles should be evaluated in concert, especially in patients with hyperkinesis. Popply chin dimpling (peau d’ orange) is frequently seen with hyperkinesis on the paralyzed side or over compensation on the unparalyzed side. Injection is usually initiated with 3 units of Botox. It is important to stay below the mental crease in the fleshy part of the men­ talis closer to the midline to avoid inadvertent weakening of the adjacent DLI. The permanent mouth frown extend­ ing to the marionette lines is caused by the depressor action of the DAO. The DAO partially overlies the DLI and caution must be used to avoid inadvertent injection of both muscles. Safe DAO injection can be performed with a starting dose of 3 units at the posterior aspect of the muscle belly, just above its insertion on the mandible at a point 1  cm lateral to the oral commissure. The contribution of the platysma muscle to facial synkinesis has long been underappreciated.99 In many individuals, fibers of the platysma muscle interdigitate with the depressor muscles of the lower lip (Figs. 40.31A and B). Hyperkinesis of the platysma may lead to oral commissure droop and exacer­ bate cervico­facial synkinesis. Vertical bands can be manu­ ally palpated and three to four injections are placed along the length of the dominant band at a starting dose of 8–10 units. Addi­tional bands may be treated at the same or lower dose depending on the degree of hyperactivity. Alternate treatments for hyperkinesis following aber­ rant regeneration include selective neurectomy or more commonly, myectomy to resect the affected muscle groups and provide permanent release of muscular spasms. The

A

B

Figs. 40.31A and B: Note the direct contribution of platysma muscle fibers to the depressor anguli oris causing oral commissure droop. Platysma hyperactivity is commonly seen in oro-ocular blink synkinesis. Treatment of the platysma muscle is important to safely and effectively treat this condition.

effi­cacy of myectomy may be surveyed through preoperative planning with selective botulinum toxin treatment. Suc­ cessful treatment with a paralytic agent is helpful in identi­fying the ideal treatment algorithm for myectomy in select patients. Considerations may include partial resec­ tion of the zygomatic major muscle to correct nasolabial spasm caused by sustained hypertonic contracture of this muscle group.100 In cases where the upper lip is retracted superiorly, the levator labii superioris muscle may be addressed.3 This effectively treats the exaggerated canine smile or excessive lateral incisor show (Figs. 40.32A to G). Prominent chin dimpling can be treated by injection or resection of the mentalis muscle. Resection of the DLI may be used to improve symmetry by inhibition of lower lip depression on the normal side, especially in patients seeking a permanent result after success with chemodenervation.82 Platysma spasm with tonic contracture may worsen lower lip contracture or result in cervicofacial synkinesis.3 Signi­ ficant success with platysmectomy is seen in patients who have a good result after platysmal chemodenervation.99

Treatment of the Contralateral Face The impact of functional treatment of the contralateral face should not be underestimated. Treatment of the procerus, corrugator, and frontalis muscle on the unparalyzed side is highly effective in treating muscle overcompensation and balancing the upper third of the face. Chemodener­ vation of the DLI has effectively been used to balance the smile without oral incompetence or speech abnormalities in the majority of patients.82 However, a small percentage

Chapter 40: Facial Nerve Reanimation

A

B A

701

C

D

E

F

G

Figs. 40.32A to G: (A to D) Evaluation of patient with right hyperkinetic facial paralysis for serial Botox chemodenervation. (E to G) Follow-up evaluation of right hyperkinetic facial paralysis for serial dosing after first Botox chemodenervation. (A) Smile: Note the hyperkinetic levator labii superioris (LLS) causing upper lateral incisor show, hyperkinetic depressor anguli oris (DAO) causing oral commissure droop, hyperkinetic mentalis muscle causing chin dimpling. (B) Eyebrow raise: Note right paralyzed brow with left facial overcompensation. (C) Lip pucker: Note involuntary narrowing of the right palpebral aperature, failure of the right hyperkinetic mentalis to assist in elevation of the lower lip, left mentalis overcompensation. (D) DOSE TITRATION 1: Left frontalis/corrugator/procerus (15 u), Bilateral orbicularis oculi (6 u each), Right LLS (2 u), Bilateral mentalis (3 u each), Right DAO (3 u), Left risorius (3 u). (E) Smile: Note the hyperkinetic LLS continues to cause upper lateral incisor show, hyperkinetic DAO causing oral commissure droop has partially improved, hyperkinetic mentalis muscle causing chin dimpling has partially improved. (F) Eyebrow raise: Brow symmetry established without causing pseudoblepharoptosis. Relaxation of the right orbicularis oculi with slight lateral brow elevation and widening of the palpebral fissure. Partially improved symmetry with softening of the left risorius and left mentalis muscles. (G) DOSE TITRATION 2: Right LLS (3 u), Bilateral mentalis (3 u), Right DAO (3 u), Left risorius (3 u).

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Otology/Neurotology/Skull Base Surgery

of patients may not find further lip weakening acceptable. A trial injection of approximately 2 mL of 2% lidocaine is commonly used to simulate the effects of contralateral weakening prior to chemodenervation.82,100 Additional treatment is commonly performed to soften the appear­ ance of the face and optimize symmetry. Caution must be taken when treating the lip elevators on the unparalyzed side for the high risk of speech disturbance that may ensue. Many patients rely on the overcompensation of the unin­ volved side to purse their lips, articulate, and maintain oral competence. This is especially true in the central lip, where treatment of the normal labii superioris alaeque nasi and zygomaticus minor may greatly disturb lip compensation. Balancing treatment on the unparalyzed side should be initiated further laterally at 1 unit increments in the area of the zygomaticus major and 2–3 unit increments in the risorius where muscle weakness remains more forgiving.

Physical Therapy and Rehabilitation The effectiveness of facial exercises and physical rehab­ ilitation for the treatment of facial paralysis has been debated for decades. Objections to facial rehabilitation stem from historic electrical stimulation protocols and maximal effort facial exercises thought to be ineffective and perhaps even harmful, leading to increased facial syn­ kinesis.10,27 Reports of modern day success highlight the impor­ tance of slower, small movement strategies, and mirror biofeedback to reinforce desired pathways and inhibit the undesirable movements of synkinesis and mass move­ ment. Physical therapy for the optimization of facial movement and facial balance is important in patients with hypertonic paralysis, facial synkinesis, and other forms of incomplete facial paralysis. Most agree that the early stimulation of flaccid muscles in complete facial paralysis is ineffective and not advised.27,101 Neuromus­ cular retraining should be deferred until the first sign of recovery is present to reduce the progression of aberrant movements and improve overall function.3,27,101 Patients with flaccid facial paralysis and asymmetry at rest should be advised to avoid overuse compensation of the uninvolved side. At the first sign of voluntary move­ ment, EMG and/or mirror biofeedback is used to rein­ force small desirable symmetric movements. Re-education stra­tegies are practiced in front of a mirror to help avoid unwanted movement patterns. Patients who have hyper­ tonic contractions are also concurrently treated with deep soft tissue mobilization and meditation-relaxation strate­ gies.27 Once a regimen is determined, home programs are

monitored at regular intervals by a trained physical thera­ pist to re-evaluate progression, impairments, and ongoing goals. Synkinesis and faulty nerve regeneration is a chronic sequelae of facial paralysis that remains responsive to cere­ bral adaptation through neuromuscular retraining, even decades after the injury.101

CONCLUSION It is difficult to review the outcomes of facial reanimation procedures given the high variability of patient grading systems, low numbers, and inherent biases relating to patient and procedure selection. Controversies remain regarding the best options; however, most would agree no one technique has evolved into the gold standard. Patient and surgeon preferences remain important fac­ tors in determining the appropriate course of treatment. Many patients are not candidates for neural or neuromus­ cular reconstruction for a variety of reasons but may still benefit from static reanimation and other ancillary proce­ dures that should not be overlooked. Treatment of the eye remains universal and corneal protection is paramount. Trends in neural substitution continue to rely on crossfacial nerve grafting and masseter nerve substitution to provide donor input in a variety of clinical scenarios. Cur­ rently, the biggest limitation remains determining when it is safe to intervene early enough to prevent the pro­ blems associated with delays in return of function includ­ ing nerve fibrosis, muscle atrophy, and increased risk of synkinesis. When prolonged denervation time and axonal load is in question, adjunct or babysitter procedures involv­ ing the hypoglossal or masseter nerve are recommended for the prevention of muscle atrophy and improvement of function. The contralateral facial nerve will always be the theoretic first choice for donor nerve because of its ability to provide symmetric, spontaneous neural input. The con­ tralateral facial nerve remains the nerve of choice to power free-muscle transfer in the pediatric population because of better regeneration outcomes seen in this population. In less than ideal scenarios, the axonal load may be insuffi­ cient with CFNG and the masseter nerve remains the next best choice. The masseter nerve is able to provide rapid reinnervation and stronger lateral commissure excursion when used to power native or freely transferred muscle. Masseter innervation exhibits close facial kinetics with facial innervation, and cortical adaptation has been shown to result in emotional smile activation after mas­ seter nerve substitution and neuromuscular retraining. Modern day techniques have evolved to reanimate facial

Chapter 40: Facial Nerve Reanimation zones separately to prevent mass movement and minimize synkinesis. In this scenario, cross-facial nerve grafting and masseter nerve or modified hypoglossal nerve substitu­ tion may be used concurrently. The limitations of dynamic reanimation can be addressed by static and ancillary pro­ cedures to balance asymmetry and support orbital, nasal, and oral function. In all cases of reanimation, appropriate use of neuromuscular retraining in concert with selective chemodenervation has been shown to suppress undesir­ able movements, reinforce desired pathways, and signifi­ cantly improve outcomes.

ACKNOWLEDGMENT Special thanks to Angelique Petropouleas for her invalu­ able assistance in preparation of this manuscript.

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49. Knox CJ, Hohman M, Kleiss I, et al. Facial nerve repair: fibrin adhesive coaptation versus epineurial suture repair in a rodent model. Laryngoscope. 2013;123:1618-21. 50. Bacciu A, Falconi M, Pasanisi E, et al. Intracranial facial nerve grafting after removal of vestibular schwannoma. Am J Otolaryngol. 2009;30:83-8. 51. Faris C. Lindsay R. Current thoughts and developments in facial nerve reanimation. Curr Opin Otolaryngol Head Neck Surg. 2013;21:346-52. 52. Divi V, Deschler DG. Reanimation and rehabilitation of the paralyzed face in head and neck cancer patients. Clin Anatomy. 2012;25:99-107. 53. Hanasono M, Silva A, Schoracki R, et al. Skull base recons­ truction: an updated approach. Plast Reconstr Surg. 2011; 128:675-86. 54. Crumley RL, Armstrong WB, Byrne PJ. Rehabilitation of facial paralysis. In: Cummings CW, et al. (eds), Cummings otolaryn­ gology—head & neck surgery. Philadelphia, PA: Mosby; 2005:822-52. 55. Best TJ, Mackinnon SE, Evans PJ, et al. Peripheral nerve revascularization: histomorphometric study of small and large caliber grafts. J Reconstr Microsurg. 1999:15(3): 183-90. 56. Hadlock T, Cheney M. Single-incision endoscopic sural nerve harvest for cross face nerve grafting. J Reconstr Microsurg. 2008;24(7):519-23. 57. Kumar S, Jacob J. Variability in the extent of sensory deficit after sural nerve biopsy. Neurol India. 2004;52(4):436-8. 58. Ozsoy U, Hizay A, Demirel B, et al. The hypoglossal-facial nerve repair as a method to improve recovery of motor function after facial nerve injury. Annals Anat. 2011; 193:304. 59. Meltzer N, Alam D. Facial paralysis rehabilitation: state of the art. Curr Opin Otolaryngol Head Neck Surg. 2010; 18:232-7. 60. Scaramella LF. The anastomosis between the two facial nerves. [Article in Italian] Arch Ital Otol Rinol Laringol Patol Cervicofacciale. 1971;82:209-15. 61. Terzis JK, Tzaffetta K. The “babysitter” procedure: mini­ hypoglossal to facial nerve transfer and cross-facial nerve grafting. Plast Reconstr Surg. 2009;123:865-76. 62. Faria JC, Scopel GP, Ferreira MC. Facial reanimation with masseteric nerve: babysitter or permanent procedure? Preliminary results. Ann Plast Surg. 2010;64:31-4. 63. Hontanilla B, Gomez-Ruiz R. Masseter nerve as “babysitter” procedure in short-term facial paralysis. Eur J Plast Surg. 2010;33:227-9. 64. Bianchi B, Copelli C, Ferrari S, et al. Facial animation with free-muscle transfer innervated by the masseter motor nerve in unilateral facial paralysis. J Oral Maxillofac Surg. 2010;68:1524-9. 65. Shipchandler T, Seth R, Alam D. Split hypoglossal-facial nerve neurorrhaphy for treatment of the paralyzed face. Am J Otolaryngol Head Neck Med & Surg. 2011;32: 511-6. 66. Manni J, Beurskens C, Van de Velde C, et al. Reanimation of the paralyzed face by indirect hypoglossal –facial nerve anastomosis. Am J Surg. 2001;182:268-73.

Chapter 40: Facial Nerve Reanimation 67. Borschel GH, Kawamura DH, Kasukurthi R, et al. The motor nerve to the masseter muscle: An anatomic and histomor­ phometric study to facilitate its use in facial reanimation. J Plastic Reconstr Aesthetic Surg. 2012;65:363-6. 68. Lee E, Hurvitz K, Evans G, et al. Cross-facial nerve graft: past and present. J Plast Reconstr Aesthet Surg. 2008;61:250-6. 69. Anderl H. Reconstruction of the face through cross-face nerve transplantation in facial paralysis. Chir Plast. 1973;2: 17-46. 70. Terzis JK, Kalantarian B. Microsurgical strategies in 74 patients for restoration of dynamic depressor muscle mechanism: a neglected target in facial reanimation. Plasg Reconstr Surg. 2000;105:1917-34. 71. Tomita K. Hosokawa K. Yano K. Reanimation of reversible facial paralysis by the double innervation technique using an intraneural-dissected sural nerve graft. J Plast Recostr Aesthet Surg. 2010;63:e536-9. 72. Heineke H. Die direkte einpflanzung der nerven in den muskel. Zentrabl Chir. 1914;41:465-6. 73. Terzis JK, Karypidis D. Outcomes of direct muscle neu­ rotization in pediatric patients with facial paralysis. Plast Reconstr Surg. 2009;124:1486-98. 74. Alex J, Toriumi DM. Permanent facial paralysis. In: Gates GA (ed). Current therapy in otolaryngology-head & neck surgery, 6th edn. St. Louis, MO: Mosby; 1998:125-9. 75. Terzis J, Olivares FS. Mini-temporalis transfer as an adjunct procedure for smile restoration. Plast Reconstr Surg. 2009; 123:533-42. 76. May M. Muscle transposition techniques: temporalis, mas­ seter and digastric. In: May M, Schaitkin BM (eds), The facial nerve, 2nd edn. New York: Thieme; 2000:635-65. 77. Cheney ML, McKenna MJ, Megerian CA, et al. Early tem­ poralis muscle transposition for the management of facial paralysis. Laryngoscope. 1995;105:993-1000. 78. McLaughlin CR. Surgical support in permanent facial paralysis. Plast Reconstr Surg. 1953;11:302-14. 79. Labbe D, Hault M. Lengthening temporalis myoplasty and lip reanimation. Plast Reconstr Surg. 2000;105:1289-97. 80. Boahene KD. Principles and biomechanics of muscle ten­ don unit transfer: application in temporalis muscle tendon transposition for smile improvement in facial paralysis. Laryngoscope. 2013;123:350-5. 81. Sidle D, Simon P. State of the art in the treatment of facial paralysis with temporalis tendon transfer. Curr Opin Otolaryngol Head Neck Surg. 2013;21(4):358-64. 82. Lindsay R, Edwards C, Smitson C, et al. A systematic algo­ rithm for the management of lower lip asymmetry. Am J Otolaryngol. 2011;32(1):1-7. 83. Hadlock T, Malo J, Cheney M, et al. Free gracilis transfer for smile in children. Arch Facial Plast Surg. 2011;13(3):190-4. 84. Zuker RM, Goldberg CS, Manktelow RT. Facial animation in children with Möbius syndrome after segmental gracilis muscle transplant. Plast Reconstr Surg. 2000;106:1-8; dis­ cussion 9.

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85. Sahin S, Yaman M, Mungan SR, et al. What happens in the other eye? Blink reflex alterations in contralateral side after facial palsy. J Clin Neurophysiol. 2009;26:454-7. 86. Hadlock T, Urban L. Toward a universal automated facial measurement tool in reanimation. Arch Facial Plastic Surg. 2012;14(4):277-82. 87. Navarrete-Alvaro M, Junyent J, Torrent L. Botulinum toxin and facial palsy. Our experience. Acta Otorrinolaringol Esp. 2010;61(4):277-81. 88. Terzis JK, Karypidis D. Therapeutic strategies in post-facial paralysis synkinesis in adult patients. Plast Reconstr Surg. 2012;129:925e-39e. 89. Booth, AJ, Murray A, Tyers AG. The direct brow lift: efficacy, complications and patient satisfaction. Br J Ohthalmol. 2004;88:688-91. 90. Costantino P, Hiltzik D, Moche J. Minimally invasive brow suspension for facial paralysis. Arch Facial Plast Surg. 2003; 5:171-4. 91. Dutton JJ. Direct brow elevation. In: Atlas of oculoplastic and orbital surgery. Philadelphia, PA: Wolters Kluwer/ Lippincott Williams & Wilkins Health; 2013:72-3. 92. Dutton JJ. Eyelid shortening by lateral tarsal strip fixation. In: Atlas of oculoplastic and orbital surgery. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins Health; 2013:108-9. 93. Patel M, Shapiro M, Spinelli H. Combined hard palate spacer graft, midface suspension, and lateral canthoplasty for lower eyelid retraction: a tripartite approach. Plast Reconstr Surg. 2005;115:2105-14. 94. Yu K, Kim AJ, Tadros M, et al. Mitek Anchor augmented static facial suspension. Arch Facial Plast Surg. 2010;12(3): 159-65. 95. Alam D. Rehabilitation of long standing facial nerve paraly­ sis with percutaneous suture based-slings. Arch Facial Plast Surg. 2007;9:205-9. 96. Mehta R, Hadlock T. Botulinum toxin and quality of life in patients with facial paralysis. Arch Facial Plast Surg. 2008;10(2):84-7. 97. Ravenni R, De Grandis D, Mazza A. Conversion ratio between Dysport and Botox in clinical practice: an over­ view of available evidence. Neurol Sci. 2013;34(7):1043-8. 98. Patel BCK, Anderson RL, May M. Selective myectomy. In: May M, Schaitkin BM (eds), The facial nerve, 2nd edn. New York: Thieme; 2000:467-81. 99. Henstrom D, Malo J, Cheney M, et al. Platysmectomy: an effective intervention for facial synkinesis and hyper­ tonicity. Arch Otolaryngol Head Neck Surg. 2011;13(4): 239-43. 100. Birgfield C, Neligan P. Surgical approaches to facial nerve deficits. Skull Base. 2011;21(3):177-84. 101. Lindsay R, Robinson M, Hadlock T. Comprehensive facial rehabilitation improves function in people with facial paralysis: a 5 year experience at the Massachusetts Eye and Ear Infirmary. Phys Ther. 2010;90(3):391-7.

Index Note: Page numbers followed by f and t indicate figures and tables, respectively.

A AAO-HNS formula 302 Abducens palsy recovery 223 Aberrant synkinesis 663 Abscess formation 225 Acellular keratin debris 179 Acoustic and ossicular coupling to hearing reconstruction 44 Acoustic neuroma 21 Acousticofacial primordium 617 Acoustic reflex decay 29, 421 Acoustic reflexes 27 Acoustic reflex thresholds 29, 421 Acoustic stimulation 569 Acquired cholesteatoma 106, 109 Acute mastoiditis 221 Acute neural injury 669 Acute otitis media (AOM) 219 Adeno-associated virus (AAV) 603 Adenoid cystic carcinoma 131 Adjunctive reanimation procedures 427 Advanced combination encoder 557 Afferent sensory fibers 627 Ageotropic nystagmus 507 Alexander’s law 71 Aloe vera 125 Alport’s syndrome 254 American Academy of Audiology (AAA) 19 American Medical Association 302 American National Standards Institute 21 American Occupational Medicine Association (AOMA) Committee 286 American-Speech-Language-Hearing Association (ASHA) 19 Amplitude of a vibration 38 Amplitude of the wave 39 Anatomy and physiology of the auditory system 1 auditory cortex 16 external auditory canal 2 inner ear 10 internal auditory canal 13 middle ear 4 pinna (auricle) 1 tympanic membrane 3

Index.indd 707

Anatomy and physiology of the facial nerve 617 central neuronal pathways 618 cerebellopontine angle 621 facial nucleus and brainstem 620 nervus intermedius 620 supranuclear pathways 618 embryology 617 extratemporal development 617 intratemporal development 617 postnatal development 618 facial nerve physiology 624 anatomic considerations 624 classification of facial nerve degeneration 624 intratemporal nerve pathways 621 internal auditory canal 621 labyrinthine segment 621 peripheral facial nerve anatomy 623 tympanic segment 622 vertical, descending, or mastoid segment 622 Anatomy of the facial nerve 667f Anatomy of the pinna 119f Angular vestibulo-ocular reflex 60 Annular ligament 10, 44 Annular rim 43 Anterior canal wall 206 Anterior malleolar fold 5, 7 Anterior malleolar ligament 4 Anterior pinna 1 Anterior tympanic artery 4 Anteroinferior canal 3 Antibiotic therapy 220 Anticompensatory eye movement 67 Apical petrositis 113 Apoptotic cascade 596 Arachnoid cysts 428 imaging 428 pathogenesis 428 treatment 428 Arachnoid villi 653 Areolar layer 1 Arnold’s nerve 3, 8, 244 Arteriovenous fistulas (AVF) 444 Asymmetric brow ptosis repair 687 Asymmetric loudness 541

Asymptomatic fistulas 650 Asymptotic hearing loss 289 Audiology threshold 655 Audiometric selection criteria 548 Audiometric testing 562 Audiovestibular and facial nerve testing 420 audiometry 420 electroneuronography 421 vestibular testing 421 Auditory brainstem implants 573 device 576 expanded applications for the ABI 577 neurofibromatosis type 2 573 patient selection 574 results 577 surgical technique and anatomy of the cochlear nucleus 574 Auditory brainstem response 31, 540, 568 measurement 540 Auditory brainstem response testing 421 Auditory brainstem tests 19 Auditory cortex 16 Auditory evoked potentials (AEPs) 20 Auditory hallucinations 379 Auditory nerve 557 Auditory skills 534 Auditory steady-state response testing 421 Auditory tube 88 Aural rehabilitation and hearing aids 529 amplification in rehabilitation 535 ALDs/Bluetooth options 538 CROS/BiCROS hearing aids 538 hearing aids 535 auditory training 533 communication training 534 counseling patients with hearing loss 531 evaluation 538 fitting 539 follow-up/problems 540 formulating an audiologic rehabilitation plan 529 goals of communication therapy 532 tinnitus management 540 utilization of vision 532 Auricular artery 3

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708

Otology/Neurotology/Skull Base Surgery

Auriculotemporal nerve 1, 3 Auspitz sign 128 Autogenous donor graft 675 Autoimmune hearing loss 582 Avascular plane 208 Axonotmesis 628

B Bacterial meningitis 225 Bacterial toxins 581 Balance rehabilitation 487t Balance system 480 Baroreceptors 85 Barotrauma 581 Basal cell carcinomas 107 Basic concepts in mechanics of hearing 40 Basic concepts in vibration 37 Basilar membrane 11 Basilar skull fractures 346 Basisphenoid bone 83 Battle’s sign 346 Beaver Dam study 318 Behavioral modification 488 Bell’s palsy 101, 115, 161, 629, 641, 664 Bell’s phenomenon 671 Benign paroxysmal positional vertigo 69, 495, 505 clinical findings 506 evaluation 507 additional studies 507 pathogenesis 506 prognosis 510 treatment 507 medical 507 surgical 509 Bezold’s abscess 221 Bilateral vestibular schwannomas (VS) 573 Bill’s bar 628 Blair incision 680 Blockage of axoplasmic flow 624 Blood vessels 583 Blue mountain study 318 Bluetooth technology 535 Bondy operation 190 Bone-anchored hearing devices 550 alpha 2 system 553 Baha systems 550 Ponto system 551 Bone-anchored hearing systems (BAHS) 569 Bone conduction thresholds 561 Bone wax 94 Bony canal wall 206 Bony cartilaginous junction 2

Index.indd 708

Bony internal auditory canal 664 Bony labyrinth 63 Bouton fibers 65 Bovie electrocautery 208 Brain abscesses 228 Brain fungus 459 Brain hernia 459 Brain parenchyma 228 Brain prolapse 459 Brainstem 65 Brainstem auditory evoked response 31 Brainstem compression 363 Brainstem evoked response 31 Branchio-oto-renal syndrome 254 Brisk venous bleeding 195 Brown’s sign 152 Brow ptosis 687 Brow skin 687 Buccal branch 619f Buccal nerve branches 681 Bundles of axons 668

C Cahart’s notch 234f Calculating hearing impairment 301 Caloric nystagmus 69 Caloric testing 33 Calyceal afferent nerve fibers 65 Calyceal fibers 65 Canal of Cotugno 13 Canal of Huguier 4 Canal wall 191 Canthal ligaments 691 Carbonic anhydrase inhibitors 379 Cardiovascular health 269 Carhart-Jerger method 19 Carhart-Jerger procedure 21 Caroticotympanic nerves 4 Carotid angiography 352 Carotid artery dissection 143 Cartilage graft 208 Cartilage overlay over prosthesis 52 Cartilaginous canal 3 Cartilaginous eustachian tube 89 Cartilaginous fracture 91 Cartilaginous skeleton 88 Catenary lever 10 Cauda helicis 1 Cavity reconstruction 191 Cell damage 585 Cellular anatomy of the peripheral vestibular sensory system 57 Cellular criteria 152 Centers for Disease Control 20 Central and peripheral zones 63 Central vertigo 517

cerebellar ataxia syndromes 524 autosomal dominant ataxias 524 autosomal recessive ataxias 524 cervical vertigo 525 clinical evaluation of the dizzy patient 517 migraine-associated vertigo 518 multiple sclerosis 525 tumors 526 vascular of vertigo 521 cerebellar stroke 524 dorsolateral pontine syndrome 524 lateral medullary syndrome 523 patterns of vascular disruption 523 Cerebellar artery 12 Cerebellar peduncles 574 Cerebellopontine angle (CPA) 101, 149, 364, 419, 627 anatomy 419 clinical findings 420 Cerebral hernia 459 Cerebral plasticity 670 Cerebrospinal fluid (CSF) 194, 350 Ceruminous adenocarcinoma 132 Ceruminous adenoma 131 Cervical branch 619f Cervical platysma 687 Cervical spinal injuries 352 Cervical vestibular evoked myogenic potentials 511 Changes in prosthesis or ossicular mass 49 Changes in the TM stiffness and mass 48 Changing the prosthesis tension 49 Characteristics of rhabdomyosarcoma subtypes 248t Chemodectomas 651 Chemoreceptors 85 Cholesteatoma 21, 179 laboratory, otologic, and neurotologic testing 182 pathogenesis 180 prognosis 192 complications of surgery 194 complications of the disease 195 recurrent and residual disease 192 results of surgery 192 radiologic imaging 182 symptoms and signs 181 diagnosis 181 treatment 183 atticotomy 185 CWD mastoidectomy 189 CWU mastoidectomy 187 tympanoplasty 183 Cholesteatoma matrix 179, 193 Cholesterol granuloma 114, 115f

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Index Chondrosarcoma 168 Chorda tympani 3 Chorda tympani injury 566 Chorda tympani nerve 4, 5, 623 Chronic neural injury 669 cohort 670 Chronic orbital sequelae 687 Chronic otitis media (COM) 8, 87, 222 Chronic rhinosinusitis 88 Cilia deflection 10 Ciliary neurotrophic factor 602 Cisplatin ototoxicity 597 Clinical relevance of damping 53 Clinical relevance of high- and low frequency middle ear function 47 Clinicopathologic classification of nerve injury 624 Coalescent otomastoiditis 109 Cochlea 102 Cochlear anatomy 356 Cochlear aqueduct 10, 58 Cochlear artery 12 Cochlear damage 270 Cochlear dehiscence 499 otologic and neurotologic testing 500 pathogenesis 499 prognosis 500 radiographic imaging 500 symptoms and signs 500 treatment 500 Cochlear duct 342 Cochlear fistulae 198 Cochleariform process 6, 622 Cochlear implantation 356, 565 Cochlear implants 557 candidacy assessment and patient selection 561 audiologic assessment 561 medical evaluation 562 patient counseling and expectations 563 radiologic evaluation 563 cochlear implant technology 557 hardware 559 software technology 557 emerging and unique populations 568 candidacy and outcomes in auditory neuropathy spectrum disorder 568 patients with low-frequency residual hearing 569 patients with single-sided deafness 569 outcomes following cochlear implantation 566 outcomes in children under 1 year of age 567 outcomes in elderly patients 568

Index.indd 709

surgical considerations 563 complications 566 surgical procedure for patients with normal cochlear anatomy 563 Cochlear nerve 14 Cochlear neurons 13 Cochlear nucleus complex 573 Cochlear promontory 444, 564 Cochlear ramus artery 12 Cochlear status 32 Cochleo-saccular hydrops 71 Cochleosacculotomy 342 Cochleovestibular abnormalities 565 Cochleovestibular anatomy 566 Cochleovestibular injury 349 Cochleovestibular nerve complex 620 Cochleovestibular nerves 621 Code of Ethics 20 Cofactors associated with occupational hairing loss 295 aspirin 295 industrial solvents 295 nonoccupational noise exposure 295 smoking 295 Cogan’s syndrome 259 Combination therapy 89 Compensation Act 302 Complex sound processing 558 Complication of suppurative otitis media 225 Complications of temporal bone infection 219 brain abscess 228 extradural/epidural abscess 224 facial paralysis 223 labyrinthitis 223 mastoiditis 219 otitic hydrocephalus 227 otitic meningitis 225 otogenic lateral sinus thrombosis 225 petrous apicitis 221 subdural empyema 228 subperiosteal and Bezold’s abscess 221 Compound action potential (CAP) 351 Concept of perceptual pitch 579 Conchal bowl 1 Conchomeatal skin flap 192 Concomitant otologic diseases 505 Conductive hearing loss 355 Congenital anomalies of the external ear 121 atresia and stenosis of the EAC 122 clinical findings 122 evaluation 123 treatment 123

709

first branchial cleft anomalies 123 clinical findings 123 pathogenesis 123 treatment 124 microtia 121 clinical findings 121 treatment 122 pathogenesis 121 protruding ears 122 clinical findings 122 complications 122 treatment 122 Congenital cholesteatoma 108, 182 Congestive heart failure 568 Contraindications for stapedectomy 237t Contralateral nostril 88 Contralateral obliques 67 Contralateral oculomotor nuclei 68f Contralateral-routing-of-signals (CROS) hearing aid system 538 Contralateral routing of sound (CROS) 569 Contralateral vestibular labyrinth 58 Contrast-enhanced computed tomography (CT) 351 Conventional hearing aids 545 Cortical adaptation 670 Cortical innervation 619 Cortical plasticity 670 Corticobulbar tract 619f Cowden’s syndrome 422 Cranial nerve substitutions 680 Cranial neuritis 113 Cranial venous drainage system 319 Creutzfeldt-Jakob disease 202 Cross-facial interposition grafting 680 Cross-facial nerve graft (CFNG) 671, 681f Crus helicis 1 CT angiogram (CTA) 100 CT venogram (CTV) 100 Cutaneous sensory 621 Cyberknife 396 Cymba concha 204

D Damping 53 Definitive Meniere’s disease 333t Deformities of the toes 482 Degenerated nerve fibers 351 De la Cruz classification 446 Delayed extubation 568 Depressor anguli oris (DAO) 683 muscle 696f Dermatologic diseases of the external ear 128

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710

Otology/Neurotology/Skull Base Surgery

atopic dermatitis 128 clinical findings 128 differential diagnosis 128 general considerations 128 pathogenesis 128 treatment 128 contact dermatitis 129 clinical findings 129 general considerations 129 pathogenesis 129 treatment 129 glandular tumors of the EAC 131 classification 131 clinical findings 132 treatment 132 osteomas and exostoses of the EAC 132 clinical findings 132 general considerations 132 treatment 132 psoriasis 128 clinical findings 128 general considerations 128 pathogenesis 128 treatment 128 Diagnosis of petrous or petrositis 222 Diamond burrs 381 Digastric muscle transfer 685 Dilatory dysfunction 86, 89 Direct brow lift 687 Direct inner ear injection 599 Diseases of the external ear 119 anatomy 119 innervation 119 lymphatic drainage 120 morphology 119 skin 119 vascular supply 120 embryology 120 physiology 120 Dix-Hallpike position 69 Dix–Hallpike procedure 507 Dizziness handicap inventory scores 512 Dural sinuses 421 Dynamic muscle transfer 683

E EAC stenosis and atresia 104 Ear canal 43, 537 Eardrum and the manubrium 51 Ectropion repair 691 Efferent neurons 65 Elastic energy 38 Electroacoustic stimulation (EAS) 569 Electrocochleography (ECochG) 32 Electrode array 560

Index.indd 710

Electrogustometry 630 Electromyographic testing 655, 669 Electroneuronography (ENoG) 630 Employees Compensation Act 302 Encephalocele 459 Encephalocele and CSF leak 459 conservative measures 468 CSF diversion 468 lumbar drain 468 ventriculoperitoneal shunt 468 histology 467 laboratory, otologic, and neurotologic testing 463 beta-2 transferrin 463 beta-trace protein 464 glucose 464 otologic, audiometric, and immittance testing 464 materials for skull base reconstruction 473 hydroxyapatite cement (HAC) 473 pathogenesis 460 congenital 461 iatrogenic 460 infectious/cholesteatoma 460 neoplastic 460 spontaneous 461 traumatic 461 prognosis 475 radiologic imaging 464 computed tomography (CT) 464 CT cisternography 466 magnetic resonance imaging (MRI) 465 MRI/MR cisternography 466 surgical approaches 468 hybrid approaches 471 middle cranial fossa (MCF) approach 469 middle ear obliteration (MEO) 472 repair of congenital CSF leak 473 transmastoid approach 468 symptoms and signs 462 treatment/prognosis 467 medical 467 surgical 467 Endaural incisions 184 Endolymphatic fluid 13 hydrops 259 sac 58 sac surgery 341 sac tumor 113f surface 62 Endolymph viscosity 64

Endolymph volumes 586 Endoneurial tubules 668 Enlarged vestibular aqueduct 15 Epidermoids 425 imaging 426 pathogenesis 425 treatment 427 Epidermoid tumors 426 Epidural abscess 224 Epidural hematoma 379 Epitympanic diaphragm 184 Epitympanic space 187 Epitympanic spaces of von Troeltsch 181 Erb’s point 676 Esteem hearing implant 549 Etiology of hydrops 331 Eustachian tube 4, 83 anatomy and physiology 83 clearance of the middle ear 85 dilation and closure 84 dysfunction 86 pathogenesis 86 signs 87 symptoms 87 evaluation 87, 88 general physiological aspects 84 middle ear gas exchange 85 patulous eustachian tube dysfunction 92 etiology 92 medical treatment 94 overview 92 pathophysiology 92 surgical treatment 94 peritubal muscles and their function 83 prognosis 91 protection of the middle ear 85 radiologic imaging 89 treatment 89 medical 89 surgical 89 Eustachian tube disorders 89 Eustachian tuboplasty 90 Evaluation for hearing instrument 538 Evaluation of auditory function 19 clinical audiologic procedures 21 acoustic reflexes 27 air and bone conduction 21 auditory brainstem responses 31 electrocochleography 32 immittance 24 otoacoustic emissions 29 speech testing 22 video nystagmography 33 demographics of hearing loss 20 future of audiology 33 scope of practice 20

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Index Evaluation of vestibular disorders 75 audiometric-based tests 79 electrocochleography 81 vestibular-evoked myogenic potentials 79 posture and gait test 79 functional gait tests 79 posturography 79 vestibular function 75 VOR tests 76 head impulse test 79 videonystagmography 76 Ewald’s First Law 67 Exostoses 106 External auditory canal (EAC) 100, 349, 491 External auditory canal wall 565 External auditory meatus 350 External canal resonance 41 External ear canal 41 External ear trauma 124 auricular burns 125 clinical findings 125 general considerations 125 treatment 125 auricular frostbite 124 clinical findings 124 pathogenesis 124 treatment 125 auricular hematoma 124 clinical findings 124 pathogenesis 124 treatment 124 auricular lacerations 124 Extraocular muscle 66 Extratemporal facial nerve 353 Extratemporal facial nerve branches 618 Extratemporal facial nerve trunk 677 Extrinsic facial nerve tumors 649 Eyelid weight implantation 673

F Facial canal 619f Facial hypertonicity 663 Facial kinetics 678 Facial musculature 628 Facial nerve 4, 14, 617 Facial nerve anatomy 629f Facial nerve canal 111 Facial nerve development 619t Facial nerve hemangioma 656f Facial nerve meningiomas 653 Facial nerve paralysis 194, 635 benign and malignant neoplasms 641

Index.indd 711

bilateral facial paralysis 641 causes 635t clinical findings 637 Bell’s palsy 637 grading facial function 637 congenital disorders 642 hemifacial microsomia 642 Möbius syndrome 642 osteopetrosis 642 evaluation 642 audiometric testing 643 electrodiagnostic testing 642 imaging studies 643 laboratory and miscellaneous testing 643 infection 640 bacterial 640 chronic otitis media 640 Lyme disease 641 malignant otitis externa 640 pathogenesis 636 prognosis 646 recurrent facial paralysis 641 trauma 639 birth injuries 639 blunt head trauma 639 iatrogenic injuries 640 penetrating injuries 640 treatment 644 medical treatment 644 surgical treatment 645 Facial nerve reanimation 663, 669 aberrant facial nerve regeneration 695 anatomy of the facial muscles 696 botulinum toxin for selective chemodenervation and ancillary procedures 697 facial synkinesis 697 physical therapy and rehabilitation 702 treatment of the contralateral face 700 evaluation 664 explaining the course of recovery 670 neurologic injury of the facial nerve 667 surgical anatomy of the extratemporal facial nerve 666 surgical planning 670 techniques 671 combined CFNG and masseter nerve or hypoglossal nerve substitution 682 cranial nerve substitution 677 direct facial muscle neurotization 682 eyelid weight implant insertion 673

711

interposition grafting 675 mobilization of the mastoid segment 676 neuromuscular transfers 683 neurorrhaphy 674 orbital management 671 static reanimation and ancillary procedures 686 Facial nerve schwannomas 427 imaging 427 pathogenesis 427 treatment 427 Facial nerve sheath 624 Facial nerve stimulating probe 381 Facial nerve testing 627 diffusion tensor tractography imaging 633 electrophysiologic testing 630 facial nerve development and anatomy 627 facial nerve physiology 628 facial nerve testing 628 intraoperative facial nerve monitoring 632 topographic testing 629 Facial nerve tumors 641, 649 clinical findings 654 extratemporal 653 intracranial tumors 653 parotid tumors 653 extrinsic lesions 651 intratemporal 651 neurotologic testing 654 pathophysiology 649 neoplasms intrinsic to the facial nerve 649 prognosis 660 radiologic evaluation 655 treatment 657 Facial paralysis 629, 641 Facial recess 4 Facial synkinesis 663, 697 Fallopian bridge approach 155 Fallopian canal 9, 158, 617, 652 Fallopian canal erosion 182 Federal Employees Compensation Laws 302 Fenestra vestibulae 4 Fibroelastic cartilage 1 Fibrous band 1 Fibrous layer 206 Fine structure processing (FSP) 557 Finite phase velocity 38 Fisch-Mattox classification 446 Fishmouth technique 680 Fissures of Santorini 3 Flaccid facial paralysis 664

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712

Otology/Neurotology/Skull Base Surgery

Flaccid muscles 702 Flaccid paralysis 663 Fluid and middle ear ventilation 50 Fogarty catheter embolectomy 227 Foley catheter 144 Foramen of Huschke 3 Foramen of Luschka 575f Fossa incudis 564 Fossa of Rosenmüller 88 FOT type reconstruction 52 Fractions of a period 39 Free-floating otoconia 69 Frey’s syndrome 8 Frontal branch facial nerve paralysis 687 Frontal lobe 619 Frontal motor cortex 627 Fulminant cochleovestibular injury 350 Fungus cerebri 459

G Gadolinium 101 Galal relaxing incisions 145 Galea aponeurosis 691 Gamma knife radiosurgery (GKR) 425 Ganglion cells 581 Gardner-Robertson classification 373 Gastric reflux 197 Gastrointestinal tract 652 Gelatinous matrix 59 Geniculate ganglion 617 Geotropic torsional nystagmus 69 Germline mutations 151 Glomus jugulare 152 Glomus jugulare tumors 153, 244 Glomus tumors 244 Glomus tympanicum 110 Glomus tympanicum tumor 245 Glossopharyngeal nerve 574, 618f Goblet cells 83 Golgi complexes 583 Golgi tendon organs 478 Gore-Tex facial slings 687 Gore-Tex slings 663 Gorlin’s syndrome 422 Gradual hearing loss with early onset 288 Granular cell tumors 650 Granular cheilitis 641 Granulation tissue 225 Granulomatous diseases 86, 88 Greater petrosal foramen 620f Greater petrosal nerve 620f Greenfield filter 144 Ground electrode 632f Guillain-Barré syndrome 641 Guinea pig 587

Index.indd 712

H

I

Hair cell (HC) ultrastructure 62f Hair cells 10 Hair follicles 3 Hallpike testing 484 Head trauma 271 Hearing aid technology 535 Hearing classification 373 Hearing protectors 296 Hearing reconstruction 44 ossicular versus acoustic coupling 44 piston diameter 44 Helix major 1 Helix minor 1 Hemangiomas 429 imaging 430 pathogenesis 429 treatment 430 Hematological malignancies 172 Hemovac drain 679 Herpes zoster oticus 112 High-riding and dehiscent jugular bulb 108 Hilger facial nerve stimulator 351 Histopathology of noise-induced hearing loss 293 History of noise exposure 269 Hochmair-Schulz-Moser sentence test 569 Holotympanic cholesteatomas 182 Homeostatic microenvironment 62 Homografts 202 Horizontal canal cupulolithiasis 507 Horizontal canal plane 58 Horizontal mattress suture 675f Horizontal nystagmus 350 Horizontal semicircular canal 33, 68f, 507, 622 Horner’s syndrome 245, 442 House-Brackmann (HB) grade I 353 House-Brackmann scale 654 of facial paralysis 664 Human cochlear duct 586 Hyaluronic acid 600 Hyaluronic acid gel 185 Hydraulic lever 10, 201 Hydraulic lever effect 201 Hydraulic lever reconstructions 53 Hydrogels and polymers 599 Hyperkinetic paralysis 664 Hypofractionated treatment delivery 397 Hypoglossal jump graft 680 Hypoglossal nerve 670 substitution 678 Hypoglossal split nerve 679 Hyrtl’s fissure 9

Idiopathic facial paralysis 631 Impedance phase 39 Implantable middle ear devices 545 esteem hearing implant 549 middle ear transducer (MET) 547 vibrant soundbridge 545 Incomplete reinnervation 663 Incudomalleolar joint 40, 47, 51, 356 Incudostapedial joint 3 Incus bar 564 Indifferent electrode 632f Infectious diseases of the external ear 125 necrotizing otitis externa 126 clinical findings 127 differential diagnosis 127 general considerations 126 pathogenesis 126 treatment 127 otitis externa 125 clinical findings 125 general considerations 125 pathogenesis 125 treatment 125 otomycosis 126 clinical findings 126 general considerations 126 pathogenesis 126 treatment 126 Inferior eyelid malposition 687 Inferior tympanic artery 9 Inferior vestibular nerve 14, 362 Infratemporal fossa 449 Inner ear 43 Inner ear anatomy 563 Inner ear fluid masses 44 Inner ear molecular therapies 581 anatomy and physiology of the round window membrane 582 anti-inflammatory drugs 597 basic concepts in inner ear damage 584 gene therapy 603 gene therapy vectors 603 RNA therapies 604 stem cell therapies 605 gentamicin in inner ear therapy 592 antioxidants 596 clinical use of gentamicin 594 otoprotection 596 inner ear drug delivery methods 598 depot injections 599 injections or bolus administrations 599 ionic inner ear mechanisms 585 neurotrophins (NTS) 598

25-06-2015 12:30:44

Index oval window permeability 584 permeability of the RWM 584 pharmacokinetics 586 regenerative and gene therapies 601 cell cycle regulation 601 role of cell death and cell replacement 602 neurotrophins 602 small molecule regulation 603 steroids in inner ear therapy 588 clinical usage of steroids 590 pharmacokinetics of steroids 588 Inner ear tissues 582 Interfaces between vibrating structures 50 Intermittent tubal dilation 84 Internal auditory artery 14 Internal auditory canal 101, 143,357 Internal auditory canal (IAC) fundus 10 Internal auditory meatus 622 Internal carotid artery 3 Internal jugular vein ligation 227 Internal maxillary artery 3 International classification of functioning 301 Interossicular fold 8 Interstitial nucleus of Cajal (INC) 60 Intra-axial lesions 431 choroid plexus papillomas and ependymomas 432 gliomas 431 hemangioblastomas 432 medulloblastomas 431 Intracanalicular component 362 Intracanalicular tumors 372 Intracranial abscess 113, 228 Intracranial cerebellopontine angle 664 Intracranial complications 228 Intracranial injury 349 Intracranial pressure (ICP) gradients 459 Intracranial vascular complications 380 Intramembranous ossification 136 Intraparenchymal abscess 228 Intrapetrous carotid artery 152 Intratemporal facial nerve 352 Intrathecal dye methods 351 Intravenous catheter 94 Ipsilateral abducens 68f ear 356 head 71 horizontal canal 68 medial rectus muscle 507 nostril 88 proximity 678

Index.indd 713

reflex 7 vestibular nucleus 68f Irregular afferents 65

J Jacobson’s nerve 4f, 8, 244 Jehovah’s Witness 141 Jerger classifications 27 Jervell-Lange-Nielson’s syndrome 254 jugular bulb 345, 385 Jugular bulb in ear disease 435 developmental and structural abnormalities 436 clinical manifestations 437 diagnostic studies 437 treatment 438 Jugular foramen 165, 421 Jugular foramen pathology 442 Jugular foramen schwannomas 448 clinical manifestations and growth patterns 449 diagnostic studies 449 pathology 449 stereotactic radiotherapy 452 treatment options 449 surgery 451 Jugular fossa 10 Jugular paragangliomas 444 Jugular venous system 145 Jugular wall 4 Jugulo-carotid spine 160

K Kartagener’s syndrome 88 Kawase’s triangle 425 Keith needle 695 Keratosis obturans 106 Kimura’s guinea pig model 331 Kinetic energy 38 Klippel Feil syndrome 15 Koebner phenomenon 128 Korner septum 187 Krauss prosthesis 212 Krebs cycle 152

L Labii superioris alaeque nasi 702 Labyrinthectomy 342 Labyrinthine artery 14, 376 fibrosis 513 fistula 194 fistulas treatment 224 segment 622

713

Labyrinthitis 111, 513 clinical findings 513 evaluation 514 radiographic tests 514 pathogenesis 513 prognosis 514 treatment 514 medical 514 Labyrinthitis ossificans 112, 513 Lagophthalmos 673 Lamellar bone 231 Langerhans’ cell histiocytosis 653 Laryngopharyngeal reflux 88, 89 Lateral cartilaginous lamina 88 Lateral epitympanic space 181 Lateral incudal fold 7 Lateral malleolar fold 7 Lateral semicircular canal 13 Lateral sinus thrombosis 226 Lateral skull base 460 Lateral tarsal strip fixation 691 Lateral tarsal strip procedure 691 Latissimus dorsi muscle 671 Leksell gamma knife 396 Lentivirus 603 Lermoyez syndrome 334 Leukotriene inhibitors 89 Levator anguli oris 667 Levator labii superioris muscle 696f, 700 Levator veli palatini (LVP) 83 Limbus vessels 12 Limitations of the audiogram 289 causes of the 4000-Hz dip 289 acoustic neuroma 290 hereditary (genetic) hearing loss 290 multiple sclerosis 291 ototoxicity 290 skull trauma 289 sudden hearing loss 290 Linear accelerator systems 396 Lipomas 429 imaging 429 pathogenesis 429 treatment 429 Lipreading 532 Longitudinally split segment 679 Longitudinal study 318 Longshore and harbor workers 302 Lotrisone lotion 199 Lower eyelid spacer graft 691 Lower facial suspension and static slings 694 Lumbar-peritoneal 378 Lumbar puncture 225, 226 Lumen of the basal turn 565

25-06-2015 12:30:44

714

Otology/Neurotology/Skull Base Surgery

Lyme disease 115, 259, 641 Lymphatic vessels 583 Lymphoid hyperplasia 88

M Macula 59 Maffucci syndrome 139, 169 Magnetic resonance spectroscopy (MRS) 423 Magnetic resonance venography 154f Malignant tumors of the temporal bone 135 evaluation 138 histology 139 pathogenesis 135 prognosis 145 surgical techniques 142 partial temporal bone resection 142 symptoms and signs 136 total temporal bone resection 143 treatment 139 Malingerer’s true thresholds 296 Malleus head 7, 548 Mammalian inner ear hair cells 581 Mandibular branch 619f Marginal vessels 12 Masseter muscle transposition flaps 683 Masseter nerve 671, 686 Masseter nerve substitution 680 Mass-spring system 38 Mastoid air cell system 219 Mastoid antrum 10 Mastoidectomies 41 Mastoid emissary vein 226 Mastoid nodes 3 Mastoid tip 548 Mattress sutures 673 Maximal stimulation testing (MST) 630 Measured phase 48 Mechanical vibrations 38 Mechanoelectrical transduction (MET) channels 61 Mechanoelectric transduction, vestibular afferent organization 57 Meckel's cave 166, 421 MED-EL device 557 Medial cartilaginous lamina 88 Medial incudal fold 7 Medial modiolar wall 565 Medial vestibular nucleus 60 Melkersson-Rosenthal syndrome 641 Membranous labyrinth 342 Meniere’s disease 21, 32, 71, 258, 331, 333t, 505, 581, 591

Index.indd 714

acute management 336 chronic management 336 aminoglycoside ablation 338 complementary and alternative medicines 340 devices 340 lifestyle adjustment, avoidance of triggers 336 pharmacologic therapy 338 rehabilitation therapy 340 salt restriction 337 steroids 339 clinical findings 333 evaluation 334 genetics 331 histology 331 management 336 pathogenesis 331 prognosis 342 radiology 335 surgical management 341 destructive surgery 342 nondestructive surgery 341 Meniere’s syndrome 236 Meningiomas 421, 452, 621 clinical manifestations and growth patterns 452 diagnostic studies 452 gross pathology 424 imaging 422 microscopic histopathology 424 pathogenesis 421 pathology 452 treatment 424 treatment options 454 Meningitis 392 Meningoencephalocele 459 Meningogenic labyrinthitis 513 Mentalis muscles 667 Merkel’s disk 479 Metastasis of the temporal bone 173 Metastatic disease 652 Metastatic lesions 430, 652 imaging 430 pathogenesis 430 treatment 431 MET carina devices 545f MET ossicular stimulator 547 Michel anomaly 111 Microphone extrusion 549 Microphone technology 537 Middle cranial fossa approach 380 Middle ear 41 Middle ear pressure gain 37 Middle ear structures 37 Middle ear transmission 51

Middle latency response (MLR) 20, 31 Midsagittal plane 58 Mid-upper lip ptosis 687 Migraines 484 Mild tinnitus 318 Minihypoglossal nerve transfer 680 Minimally invasive brow suspension 689 Mitek anchor suspension 663 Mitek anchor suture techniques 687 Möbius syndrome 642 Mohs surgical technique 130 Mondini’s malformations 15 Motor fibers 624, 627 Muckle-Wells’ disease 259 Muckle-Wells’ syndrome 255 Mucopolysaccharides 59 Multichannel cochlear implants (CIs) 557 Multifocal tumors 444 Muscle tension 478 Musical timber 534 Myriad connections 618 Myringotomy 3, 220

N Nanoparticles 600 Nasal antihistamine 89 Nasogastric tube 144 Nasolabial folds 687 National Institute for Occupational Safety and Health (NIOSH) 269 Necrotizing external otitis (NEO) 105 Necrotizing otitis externa (NOE) 126 Neoplasms of the external ear and ear canal 129 basal cell carcinoma of the auricle 129 clinical findings 129 differential diagnosis 129 general considerations 129 pathogenesis 129 staging 129 treatment 129 cutaneous squamous cell carcinoma 130 clinical findings 130 differential diagnosis 130 general considerations 130 pathogenesis 130 prevention 131 prognosis 131 staging 130 treatment 130 melanoma of the external ear 131 clinical findings 131 differential diagnosis 131 general considerations 131

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Index prevention 131 staging 131 treatment 131 Nerve excitability test (NET) 350 Nerve graft procedure 680 Nerve growth factor (NGF) 598 Nerve to stapedius 619f Nerve to stylohyoid 619f Nervus intermedius 621f, 627 Neural integrator 71 Neurofibromas 650 Neuromucocutaneous disease 641 Neuromuscular free-flap transfer 685 Neurophysiologic testing 157 Neurotransmitter glutamate 64 Neurotransmitters glycine 60 Neurovascular bundle 686 Neurovascular pedicle transfer 685 NF2-associated vestibular schwannomas 405 management 405 medical management 405 surgical management 405 Node of Ranvier 669 Noise exposure 285 Noise exposure history 291 Nonabsorbable suture 564 Nonorganic hearing loss 295 Nonotologic disorders and tinnitus 319 Non-squamous cell carcinoma tumors of the temporal bone 149 anatomy 149 chondrosarcoma 168 clinical presentation 169 diagnosis 169 pathology 169 treatment 170 differential diagnosis 149 endolymphatic sac and duct tumors 163 clinical manifestations 163 diagnosis 164 endolymphatic sac tumors 163 pathology 163 treatment 165 facial nerve schwannomas 157 clinical manifestations 157 diagnosis 157 pathology 157 treatment 158 geniculate ganglion hemangiomas 161 clinical manifestations 161 diagnosis 161 pathology 161 treatment 162

Index.indd 715

jugular foramen schwannomas 159 clinical manifestations 160 diagnosis 160 pathology 159 treatment 160 meningiomas 165 anatomic patterns 166 clinical manifestations 166 diagnosis 167 pathology 166 treatment 167 paragangliomas 149 classification 155 clinical manifestations 152 diagnosis 152 pathology 152 treatment 155 rhabdomyosarcoma 170 clinical presentation 171 diagnosis 171 pathology 170 treatment 171 Normal mode frequency 39 Notch of Rivinus 5 Nucleus prepositus hypoglossi (NPH) 60

O Occipitalis muscle 666 Occipital scalp 1 Occupational hearing loss 283 characteristics of OHL 286 audiometric features 286 federal regulation of OHL 284 development of a noise standard 284 disability and impairment 286 Occupational Safety and Health Act legislation 284 Occupational safety and health administration (OSHA) guidelines 269 Octreotide scintigraphy 444 Ocular counter-roll (OCR) 60 Ocular tilt reaction 72 Oculomotor neuron 66 Oculomotor nucleus 60 Oligodendroglial cells 362 Ollier disease 139 Optokinetic system 66 Oral commissure 694 Oral commissure malposition 687 Oral steroids 590 Orbicularis oculi muscle 624, 666, 691 Orbicularis oris 624 Organ of Corti 13, 232f, 558

715

Oro-ocular synkinesis 700 Ossicular chain 547, 629 Ossicular chain reconstruction (OCR) 199 Ossicular coupling 43 Ossicular coupling and acoustic coupling 201 Ossicular fixation-fusion 110 Ossicular lever 10, 201 Ossicular lever effect 201 Ossicular mass 44, 48 Ossicular reconstruction 189 Osteoma 106 Ostmann’s fat pad 88 OTE style hearing aid 536 Otitic hydrocephalus 227 Otitis externa 126, 545 Otitis media 88, 109, 219, 226 Otoacoustic emissions 11, 568 Otoconial mass 71 Otogenic cerebral abscesses 459 Otolithic membrane 64 Otolith organs 59 Otolith physiology 71 Otologic disorders 269 Otomycosis 126 Otosclerosis 112, 231 clinical findings 233 signs 233 symptoms 233 evaluation 234 audiologic testing 234 histology 236 radiologic imaging 235 pathogenesis 231 etiology 233 histopathology 231 pathophysiology 232 treatment 236 medical management 236 surgical management 236 Otosclerotic fixation of the stapes 53 Otospongiosis 112 Ototoxic exposure 269 Ototoxicity 307 clinical findings 311 aminoglycosides 311 cisplatin 311 DFMO 311 imatinib 311 loop diuretics 311 macrolide antibiotics 311 salicylates 311 vicodin 311 vincristine/vinblastine 312 pathogenesis 307

25-06-2015 12:30:45

716

Otology/Neurotology/Skull Base Surgery

mechanisms of aminoglycoside 308 mechanisms of cisplatin 308 mechanisms of DFMO 309 mechanisms of hydrocodone/ acetaminophen 310 mechanisms of loop diuretic 309 mechanisms of macrolide 310 mechanisms of salicylate 308 vinka alkaloid mechanisms of ototoxicity 310 prevention 312 Outer hair cells (OHCs) 10 Oval window (OW) 4, 40, 582 Overlay technique 205

P Paget's disease 139, 319t Paracusis of Willis 233 Paragangliomas 438, 651 age at presentation, multifocality and catecholamine secretion 441 clinical manifestations and growth patterns 441 diagnostic studies 442 differential diagnosis 444 history 438 malignancy and occult paragangliomas 441 molecular genetic screening 446 outcomes 448 complications 448 cranial nerve deficits 448 recurrence rates 448 pathogenesis 439 pathology 438 terminology 438 treatment 447 nonsurgical treatment 447 surgery 447 Paralytic ectropion 691 Parotid gland 679 Pars flaccida 3 Pars tensa 3 Pediatric eustachian tube 86 Pedicle muscle transfer 683 Pendred’s syndrome 15, 254 Perijugular skull base 449 Perilymphatic duct 10, 58 Perilymph fluid withdrawal 600 Perilymph leakage 565 Perilymph volumes 586 Perineural spread 140 Peripheral end organs 60

Index.indd 716

Peripheral nerve injury and regeneration 668 Peripheral vertigo 505 Peripheral vestibular disorder 33 Peritubal air cells 152, 222 Peritubal muscles 83, 85 Persistent stapedial artery 108 Petroclival synchondrosis 651 Petrotympanic (Glaserian) fissure 4 Petrous and squamous bones 4 Petrous apex 152 Petrous apex of the temporal bone 221 Petrous versus nonpetrous 346 Pharyngeal recess 88 Pharyngotympanic tube 84 Phase velocity 38 Phrenic nerves 677 Physical therapy techniques 678 Physical trauma 581 Physiologic artifact 655 Piezoelectric actuator 549 Pinna and mastoid scalp area 1 Pitanguy’s line 667 Pitch pattern 579 Pittsburgh Grading System 139 Placebo-controlled studies 331 Pontine facial nerve nucleus 669 Pontomedullary junction 627 Pöschl and Stenvers reconstructions 112 Positive lymph nodes 140 Possible Meniere’s disease 333t Postauricular artery 3 Postauricular incision 204, 548, 564 Postauricular skin grafting 122 Postauricular soft tissues 226 Postauricular wound 204 Posterior cranial fossae 345 Posterior fossa 449 Posterior fossa encephaloceles 459 Posterior lamella of the lateral canthal tendon 691 Posterior semicircular canal dehiscence 499 otologic and neurotologic testing 499 pathogenesis 499 prognosis 499 radiologic imaging 499 symptoms and signs 499 treatment 499 Postganglionic parasympathetic fibers 628 Post-traumatic functional deficits 346 Pouch of von Troeltsch 8, 9 Preganglionic parasympathetic fibers 617, 622 Presbycusis 267 clinical evaluation 272

epidemiology 268 etiology 269 additional etiological factors 270 aging and oxidative injury 269 association with dementia 271 hereditary factors 270 impact of presbycusis 271 noise 269 psychosocial impact 271 public health impact 272 management 277 auditory assistive devices 277 cochlear implants 278 environmental optimization 277 hearing aids 278 pathophysiology 272 prevention 277 Presbystasis and balance in the elderly 477 balance system 478 diagnosis of presbystasis 484 effects of aging on the balance system 479 central nervous system changes associated with age 482 effect of age on the somatosensory system 481 effect of age on the vestibular system 480 effect of age on the visual system 482 efferent changes associated with aging 483 extrinsic factors influencing dizziness and falls 483 general changes in balance associated with aging 480 examination 485 history 485 treatment 487 Pressure gain at the OW (PGOW) 45 Pressure gain transformer 42 Prevention of noise-induced hearing loss 283 Primary cholesteatomas 621 Primordial inner ear 617 Progression of hearing loss 261 Proprioception 478 Prosthesis slippage 203 Prothesis to malleus 52 Proton beam radiation 137 Prussak’s space 9, 102, 181 Pseudomonas 584 Psychogenic hearing loss 295 Psychosocial stigma 545 Pterygoid canal 628 Pterygoid plate 83

25-06-2015 12:30:45

Index Pterygopalatine fissure 155 Pterygopalatine fossa 628 Pure tone average (PTA) 22 Purulent otorrhea 138 Push-pull system 67

Q Queckenstedt’s test 226

R Radioisotope dye instillation 351 Radioisotope studies 355 Radiology of the temporal bone 99 imaging techniques 99 computed tomography 100 magnetic resonance imaging 100 plain radiography 99 normal imaging anatomy 102 axial plane 102 coronal plane 102 general concepts 102 MRI 104 pathologies of the facial nerve 114 hemangioma 115 infection 115 neoplasm 115 pathologies of the inner ear 110 congenital anomalies 110 infectious/inflammatory lesions 111 neoplasm 113 otospongiosis 112 SSCC dehiscence 112 pathology of the middle ear 107 congenital lesions 108 infection 109 inflammatory lesions 109 neoplasm 110 osseous lesions 110 vascular anomalies 107 pathology of the outer ear 104 congenital anomalies 104 infection 105 inflammatory lesions 106 neoplasm 107 osseous lesions 106 pathology of the petrous apex 113 infection 113 inflammatory lesions 114 neoplasms 114 petrous apex cephalocele 114 trauma 116 fractures 116 ossicular dislocation 116

Index.indd 717

Ramsay Hunt syndrome 112, 638, 654 Rasmussen’s bundle 13 Raynaud’s disease 93 Reactive oxygen species (ROS) 585 Recording electrode 632f Recurrent otitis media 247 Reflex activating stimulus (RAS) 27 Reflux disease 88 Region of the stylomastoid foramen 627 Reissner’s membrane 11t, 331 Resonance frequency 38 Respiratory infections 88 Retinal slip velocities 67 Retroauricular region 548 Retrocochlear lesion 29 Retrocochlear pathology 421 Retrofenestral otospongiosis 112 Retrograde jugular venography 138 Retrograde mastoidectomy 190 Retrolabyrinthine 342 Retrolabyrinthine transdural approach (RLTD) 165 Retrospective questionnaire study 547 Revised Speech Perception in Noise test 23 Rhabdomyosarcoma 168 Rinne and Weber tests 234 Risorius muscle 696f Robinow syndrome 121 Rosenthal’s canal 588 Rosetti Infant-Toddler Language Scale (RI-TLS) 567 Round window 4, 37 Round window membrane (RWM) 582 Ruffini’s endings 478 RW protection with OW access 45

S Sacculocollic reflex 71 Salvage therapy 591 Samter’s triad 86 Saphenous vein 676 Scala media 12, 587 Scala media endolymph 585 Scala tympani 10, 12, 40, 584 Scala tympani of the cochlea 4 Scala vestibuli 40, 584 Scala vestibuli of the cochlea 58 Scarpa’s ganglion 60 Scarpa’s ganglion neurons 233 Scar tissue 53 Schirmer's test 665t Schwann cells 362, 628, 649, 650 Schwannoma of the inner ear 113 Schwannomas of the facial nerve 115

717

Segment of bone 628 Semicircular canal dehiscence syndrome 93 Semicircular canals 166, 491 Sendai virus 603 Sensorineural hearing loss 253, 287, 356, 557 clinical findings 259 evaluation for audiometric testing 259 evaluation for SNHL 261 adult onset SSNHL, asymmetric and progressive SNHL 262 congenital sensorineural hearing loss 261 histology 262 pathogenesis 253 prognosis 263 treatment 262 Sensorineural hearing loss (SNHL) 557 Sequelae of a temporal bone fracture 352 Serous labyrinthitis 219 Severe trauma 352 Sex-linked nonsyndromic genes 253 SHOM type prosthesis 51 Shortest stereocilium 61 SHOT prosthesis 50 Shrapnell’s membrane 3f Sigmoid sinus 13, 143, 345 Sigmoid sinus exposure 182 Silverstein clamp 143 Single-sided deafness (SSD) 569 Singular nerve 14 Sinodural angle 192 Sinuplasty balloon 90 Sinus thrombosis 227 Sinus tympani 4, 187 Skew deviation 72 Skull base foramina 421 Sleeve resection 142 Slow-phase of nystagmus 69 Snail-like shape of the cochlea 103f Snake eye appearance 102 Somatosensory system 478 Somatotopic primate studies 619 Sound fidelity 545 Speech awareness threshold (SAT) 22 Speech detection threshold (SDT) 22 Speech discrimination testing 561 Speech-language pathologists (SLPs) 529 Speech reading 532 Speech spatial and qualities of hearing scale 569 Spheno-occipital synchondroses 651 Spheno-petrosal synchondroses 136 Spine of Henle 206 Spiral ganglion 270 Spiral ganglion cell 566

25-06-2015 12:30:45

718

Otology/Neurotology/Skull Base Surgery

Spiral ganglion neurons 13 Spiral lamina 342 Spondee recognition threshold (SRT) 22 Squama of the temporal bone 566 Squamous cell 107 Squamous epithelium 426 Squamous metaplasia 179 SSCC dehiscence 112 Stapedial muscle 7 Stapedial reflex 7 Stapedio vestibular ligament 582 Stapedius muscle 7 Stereocilia 60 bundles 61 deflection 62f Stereociliary bundles 62f, 63 Stereociliary deflection 67 Stereotactic radiotherapy 447 Sternocleidomastoid muscle 160, 495 Stiffness and mass effects in the middle ear 48 Stiffness dominated system 48 Stiffness of the prosthesis 49 Storiform pattern 249f Stylomastoid artery 3, 8, 9 Stylomastoid foramen 8, 127, 621, 622, 664 Subacute neural injury 669 Subdural empyema 228 Subjective visual horizontal (SVH) 72 Sublingual gland 620f Suboccipital approach 382 Suboccipital plate 382 Suborbicularis dissection 673 Suborbicularis oculi injections 673 Subperiosteal abscess 221, 226 Sunderland classification of peripheral nerve injury 668t Superficial musculoaponeurotic system (SMAS) 667 Superficial petrosal nerve 620 Superficial temporal artery 1 Superficial temporalis fascia 1 Superior canal dehiscence syndrome 505 Superior eyelid malposition 687 Superior oblique muscle 506 Superior semicircular canal 13 Superior semicircular canal dehiscence 491 differential diagnosis 495 otologic and neurotologic testing 494 pathogenesis 491 prognosis 498 radiologic imaging 495 symptoms and signs 493 treatment 496

Index.indd 718

Superior semicircular canal (SSCC) 100 Superior vestibular nerve 14, 365 Supralabyrinthine cell tract 222 Sural nerve 685 Sural nerve graft 681 Surgical anatomy of the greater auricular nerve (GAN) 676f Surgical removal of vestibular schwannoma 375 Surgical trauma 581 Swan-Ganz catheter 144 Sweat glands 3 Sympathetic plexus 442 Symptomatic tumor 574 Symptoms of labyrinthitis 223 Synaptic vesicles 294

T Tarsorrhaphy procedure 673 Technique of tympanoplasty 197 Tegmen erosion 182 Temperoparietal fascia 667 Temporal artery 1 Temporal bone 84, 100, 345 Temporal bone fracture 664 Temporal bone infection 219 Temporal bone studies 52 Temporal bone trauma 345 laboratory, otologic, and neurotologic testing 350 audiogram 350 electrodiagnostic testing of facial nerve 350 laboratory 351 radiologic imaging 351 vestibular testing 350 pathogenesis 345 symptoms and signs 346 treatment and prognosis 352 associated lower cranial nerve injury 357 CSF leak 355 facial nerve injury 352 hearing loss 355 vestibular injury/dysfunction 356 Temporalis fascia 564 Temporalis muscle 683 Temporalis tendon transfer 684 Temporal scalp 1 Temporary tarsorrhaphy 675f Tensa cholesteatomas 182 Tensor tympani fold 7, 83 Tensor tympani muscle 4, 622 Thornwaldt cysts 86 Tinel’s sign 685 Tinnitus 317

GABA-ergic medications for tinnitus 323 acoustic therapy 326 counseling strategies 327 electrical stimulation 327 general health strategies 328 transcranial magnetic stimulation 325 incidence and prevalence 317 laboratory, otologic, and neurotologic testing 320 medications for tinnitus 323 otologic disorders and tinnitus 319 somatic tinnitus and somatic modulation 319 temporomandibular joint disorders and tinnitus 320 tinnitus and comorbid conditions 320 typewriter tinnitus 320 pathogenesis 318 pathophysiology 322 prognosis 328 radiologic imaging 321 tinnitus duration 321 tinnitus severity 322 symptoms and signs 318 treatment 322 medical 322 surgical 322 Tinnitus evaluation 541 TM for tympanic membrane 37 TM–prosthesis interface 51 Tobey-Ayer test 226 Tongue atrophy 680 Topical anesthetic 673 Torus tubarius 84, 86, 88 Total hearing loss 573 Tractus solitarius 621f Tragal reconstruction and soft tissue debulking 122 Transitional zone 62 Translabyrinthine craniotomy 384 leaks 459 resection 386 Transmastoid labyrinthectomy 342 Traumatic facial nerve neuromas 650 Traumatic parenchymal injury 379 Traumatic scala tympani 564 Treacher Collins syndrome 15, 121 Treatment of petrositis 222 Trigeminal neuralgiform 641 Trimethylphenylammonium (TMPA) 584 Tubal orifice 86, 88 Tubal valve 94 Tullio phenomenon 493 Tumors of the middle ear 243

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Index adenomas 246 choristoma 250 glomus tumors 243 hemangiomas 247 rhabdomyosarcoma 248 teratoma and dermoid 249 Turbo spin echo (TSE) 101 Tympanic artery 3 Tympanic cavity 85, 345 Tympanic incisura 2 Tympanic isthmus 8, 181 Tympanic membrane 2, 179, 202, 345 Tympanic membrane lever effect 201 Tympanic ring 2 Tympanomeatal flap 190, 239 Tympanoplasty and ossiculoplasty 197 evaluation 197 normal anatomy and the healing process 199 ossiculoplasty 199 acoustic mechanics 200 prosthesis design 202 prosthesis development in OCR 201 prosthesis extrusion 202 prosthesis mechanics 202 prosthesis slippage 203 surgical technique of ossiculoplasty 212 alloplasts 212 autografts 212 universal prosthesis 212 surgical technique of tympanoplasty 203 cartilage tympanoplasty 208 myringoplasty 203 tympanoplasty 204 Tympanosclerotic fixation of the ossicles 53 Tympanosclerotic plaques 204 Tympanostomy tube 220

U Unilateral facial paralysis 157 Unilateral labyrinthine dysfunction 71 Unilateral labyrinthine function 65 Unmyelinated nerve fibers 274f Urinary retention 568 Usher’s syndrome 15, 254 Utricle 71

V Vaccinia virus 603 Vagus nerve 84, 651 Valsalva-evoked eye movements 494

Index.indd 719

Valsalva maneuver 92, 463 Van Hippel-Lindau syndrome 113 Vanillylmandellic acid (VMA) 153 Vascular causes of tinnitus 319 Vascular mass 444 Vascular strip 2, 3 Vascular vasospasm 356 Vasomotor rhinitis 88 Venous congestion 379 Venous infarction 379 Ventral cochlear nucleus 575 Ventriculoperitoneal 378 Vernet syndrome 152 Vertical plane 1 Vertical Y-axis 687 Vestibular ablative procedures 484 Vestibular afferents 64, 65 Vestibular anatomy 33 Vestibular aqueduct 13, 261 Vestibular-evoked myogenic potentials (VEMPs) 335, 494 Vestibular-evoked myogenic potential (VEMP) thresholds 480 Vestibular function 356 Vestibular ganglion 362 Vestibular hair cells 59 Vestibular nerve 512 Vestibular neurectomy 342 Vestibular neuritis 505, 510 clinical findings 511 evaluation 511 physical examination 511 physiologic tests 512 radiographic tests 512 pathogenesis 510 prognosis 512 treatment 512 medical 512 surgical 512 Vestibular nuclei 60 Vestibular nucleus 66 Vestibular nystagmography 562 Vestibular ocular reflex (VOR) 68f Vestibular pathology 21 Vestibular schwannoma 149, 262, 361, 362, 621 clinical manifestations 362 etiology and pathology 361 growth characteristics 362 incidence and epidemiology 361 management strategies 367 cost 368 failure rates of conservative management 371 microsurgical resection 372 natural history of untreated vestibular schwannomas 369

719

patient counseling 367 quality of life 369 radiation 395 special considerations 371 surgical outcomes 387 watchful waiting 369 rehabilitation 403 auditory rehabilitation 404 facial nerve deficit management 403 workup 364 auditory and vestibular studies 364 delayed diagnosis 367 imaging studies 366 NF2 testing 366 Vestibular schwannoma surgery 670 Vestibular structures 584 Vestibular symptoms 233 Vestibular system 57, 480 gross anatomy 57, 60 bony and membranous labyrinth 57 otolith organs 59 semicircular canals 58 vestibular neuroanatomy 60 mechanoelectric transduction 63 otolith physiology 71 physiology 57 vestibular afferent organization 65 vestibular end organs 61 crista ampullaris 62 hair cells 61 macula 63 vestibulo-ocular reflex 66 Vestibular tests 19, 365 Vestibular therapy 584 Vestibulocochlear artery 12, 60 Vestibulocochlear dysplasia 110 Vestibulocochlear injury 350 Vestibulocochlear nerves 14 Vestibulo-ocular reflex 33, 478, 511 Viable facial nucleus 671 Vibrating eardrum 37 Vibrating ossicular prosthesis 546 Vibration velocity 39f Video nystagmography (VNG) 33, 482 Vidian canal 628 Virtual channel (VC) technology 559 Visual analog scales 540 Visual communication 533t Visual field 66 Visual reinforcement audiometry (VRA) 562 Voltage-gated calcium channels 64 Von Hippel-Lindau’s (VHL) disease 163

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720

Otology/Neurotology/Skull Base Surgery

W Waardenburg’s syndrome 15, 254 Wallerian degeneration 668 Wave amplitude 39 Weber test 10 Wegener’s disease 86 Werner’s syndrome 422 White blood cell (WBC) 220 White matter edema 423 Whitnall’s tubercle 691 Word recognition measures 22 Word recognition score (WRS) 22

Index.indd 720

Workers’ Compensation Law 302 Wound infections 392 Wrisberg’s nerve 620 Wullstein’s original classification scheme 199 Wullstein’s tympanoplasty classification 44 Wullstein type III tympanoplasty 45

Y Yellow-gray heterogeneous masses 362

Z Zellballen appearance 243 Zygomatic arch 155, 667, 694 Zygomatic bone 666 Zygomatic branch 619f, 664, 666 Zygomatic branches of the facial nerve 666 Zygomatic major lip elevator 683 Zygomaticobuccal distribution 697 Zygomatic root 221 Zygomatic root cells 193 Zygomaticus major muscle 696f Zygomaticus minor muscle 696f

25-06-2015 12:30:45