Botulinum Toxin for Facial Harmony

Dedication

This book is dedicated to my parents, who with their example of life and love showed me the path that I now teach my children. I would have loved to be able to show you this book. To my brother, Antônio Eugênio Pacheco, a nature lover and the master of overcoming life’s difficulties. To my sister, Marya Olimpia Pacheco, who has found the balance between strength and tenderness and is the most ethical person I have ever met. To my beloved wife, Cláudia Bittar, for her hard work and dedication that keeps our family united. To my beloved children—Gabriel Pacheco, my best friend, and Ana Sofia Pacheco, my turning point for happiness—for all the joy they have given me.

Library of Congress Cataloging-in-Publication Data

Names: Flávio, Altamiro, author.

Title: Botulinum toxin for facial harmony / Altamiro Flávio.

Description: Hanover Park, IL : Quintessence Publishing Co Inc, [2018] | Includes bibliographical references and index.

Identifiers: LCCN 2018011314 | ISBN 9780867157871 (hardcover)

Subjects: | MESH: Botulinum Toxins, Type A--therapeutic use | Cosmetic Techniques | Facial Muscles--drug effects | Case Reports

Classification: LCC RL120.B66 | NLM QV 140 | DDC 615.7/78--dc23

LC record available at https://lccn.loc.gov/2018011314

© 2018 Quintessence Publishing Co, Inc

Quintessence Publishing Co, Inc
411 N Raddant Road
Batavia, IL 60510
www.quintpub.com

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All rights reserved. This book or any part thereof may not be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, or otherwise, without prior written permission of the publisher.

Editor: Leah Huffman
Design: Sue Zubek
Production: Sue Robinson

Printed in China

contents

Foreword by Christian Coachman

Foreword by Paulo V. Soares

Preface

01

Basic Principles of Botulinum Toxin

02

Facial Analysis and Photographic Documentation

03

Muscles: Injection Technique and Location

04

Clinical Cases

Index

Extra content

Extra content is available online. QR codes throughout the book link to PDFs, PowerPoint presentations, and videos that can be used by the professional to facilitate better treatment planning and delivery of care. Scan the QR code here to access this supplementary information. The full list of links may also be found at www.quintpub.com/BTX.

foreword

Esthetics should be considered part of dentistry as a whole instead of just a specialty. Regardless of our expertise, a common goal in dentistry will always be to integrate, preserve, or recreate function, biology, structure, and esthetics. Therefore, there is no dentistry without esthetics and no facial esthetics without dentistry.

As the well-known plastic surgeon Ivo Pitanguy once said, “Before performing facial plastic surgeries, we should first take care of the smile.” A smile works as a postcard of ourselves, a universal expression unique to human beings. Consequently, esthetics has an essential role as a means to generate self-esteem, confidence, well-being, and joy.

In order to be able to produce esthetic smiles, we first should understand the face itself. All professionals who work with smile rehabilitation should be experts on the face. We have noticed a lack of facial knowledge by dentists as well as a lack of knowledge of smiles by plastic surgeons. This gap should not exist. The integration of these two worlds will transform the way we impact people’s lives by modifying their facial expressions.

Patients who need or want more confident smiles deserve a complete orofacial analy­sis that should be made by a team of professionals with extensive knowledge in areas that include orthognathics, orthodontics, orthopedics, total prosthesis, cephalometry, dentogingival esthetics, airways, occlusion, perioral procedures, dermatology, and plastic surgery procedures. Instead of elaborating esthetically perfect projects, it is essential to obtain harmonious results that will meet the morphopsychologic desires of our patients.

Being an orofacial expert involves more art than math—an art that produces predictable results through the detailed study of facial anatomy and clinical practice of the procedures. This explains why I became a fan of Altamiro, a pioneer and artist of orofacial esthetics. In my point of view, this book will become a reference on this topic due to the great skill of the author in organizing and expressing his ideas, his vast clinical experience, his wonderful results achieved, and his educational method used to gather all of his knowledge. Without a doubt, this masterpiece will help all dentists who wish to go beyond their current scope. For all these reasons, it is a great honor to introduce this book. Best wishes and good luck in this journey.

Christian Coachman, DDS, CDT
Founder of Digital Smile Design

foreword

The challenge of our generation is to look young and youthful for the longest time possible. Botulinum toxin (BTX) is useful in the treatment of many diseases. Dental clinicians are experts on the head and neck area and have a deep comprehension of the anatomy and physiology of the muscles of the face. BTX has been applied in conjunction with hyaluronic acids for the treatment of facial asymmetry, temporomandibular disorders and facial pain, bruxism and clenching, and age-related or other esthetic concerns. The clinical application of BTX can help to control parafunctional habits, improve facial esthetics, and altogether change patients’ quality of life.

It is my pleasure to introduce this book written by my mentor on this subject, Dr Altamiro Flávio. The book is divided between the fundamental concepts of BTX application and protocols to use in various clinical situations. This handbook is designed to be a practical introductory and reference guide for students, clinicians, and researchers. The author has gathered the necessary knowledge, clinical fundamentals, scientific evidence, and technical skills and protocols to write the constituent chapters.

I hope you enjoy this book and can achieve success with BTX application in your patients.

Paulo V. Soares, DDS, MS, PhD
School of Dentistry
Federal University of Uberlândia, Brazil

preface

Throughout these 25 years working as a teacher, sometimes I catch myself rereading old educational materials, and I find that the only knowledge we keep is that which we use in our daily practice. This book was based on this concept. All information provided has clinical applicability. When you are 50 years old, it is only natural to start evaluating what is really worthwhile in life. My goal was to write an objective book that could effectively guide professionals who want to provide the different benefits of botulinum toxin to their patients. Even before thinking about treating a patient, we as professionals must concentrate on not causing any injury, so I chose to describe the limits and risks of the most delicate procedures. Science has several theories, some feasible and others not so much. This fact has always confused readers of scientific works. Therefore, I was cautious enough to prove several of the contents in the book through numerous clinical cases, carefully retreated and described in an objective way.

My students often complain that botulinum toxin treatments only last 5 months. When they do this, I ask them to name one type of antibiotic, anti-inflammatory, anesthetic, or antidepressant that has an effect that lasts as long. In fact, the duration time is one of the greatest advantages of the toxin. I see these complaints as an acknowledgment of the toxin’s benefits and a subconscious desire for the effect to last longer.

Other students ask themselves why God in his infinite perfection did not allow all human beings to be beautiful. I posit that perhaps this was on purpose so we as humans can develop the skill to love others regardless of their outward appearance. Nonetheless, it is the professional’s responsibility to study hard to offer health and esthetics to his or her patients.

I get excited when I see the final results of treatment in my daily practice. This professional accomplishment is a great reward. I rarely have patients who are not secure enough to accept the esthetic procedures. While they understand that aging is a natural part of life, they do not want changes to their face, so these esthetic procedures allow them to maintain their appearance a little longer.

Finally, during the course of reading this book, the reader will find a lot of numbers; these numbers help us to find the correct dimensions and proportions. Because each face has different measurements, we need numbers and proportions to provide specific treatments. It is part of my philosophy to create “one smile for each face.”

God bless you all. And please enjoy the reading.

Acknowledgments

I would like to express my gratitude to Dr Paulo Vinícius Soares for the idea and encouragement to write this book. It is an honor to be trusted by this great professional. I am also grateful and have great respect for Bill Hartman, Leah Huffman, Bryn Grisham, Sue Robinson, Sue Zubek, and the entire Quintessence crew involved in giving life to this book. You amaze me with your work. My special thanks to Dr Rubelisa Cândido Gomes de Oliveira for assisting us with the scientific format of this book. Your organization is deeply appreciated. My dear Denise Riley, I am so grateful for the uncountable hours spent on finding the right terms for my books. You are like a sister to me. I wish to thank my secretary, Carina Morais, for her perfectionism and unselfish friendship. I also would like to thank my friends at the Miami Anatomical Research Center—Allan Weinstein, Eduardo Sadao, Heloise Peixoto, Justin Fraioli, Jorge Carrasco, and Maylin Perez Carrasco—for their effort in keeping up with our courses that help educate so many professionals. I wish to acknowledge my first supporter, Dr Francisco Leite Pinto, as well as my friend Dr Newton Fahl Jr, who taught me the meaning of “possessing the knowledge.” To my friend Dr Fernando Saad, thanks for your true friendship and for the “true vertical line.” Dr Francisco Célio Dantas, thank you so much for all those years as a partner in our mission to educate. Dr Maria Geovânia Ferreira, even after 20 years of partnership your competence still surprises me. Dear anatomists Márcia Viotti and Rogério Zambonato, you amaze all students with your skillful dissections. Congratulations! Thank you, Alberto Van Lima, for spending so many nights working hard to produce such beautiful images all these years. I also would like to express my gratitude to Professor Luis Fernando Naldi for our discussions about esthetic facial references. My grateful thanks to Professor Paula Cardoso and Rafael Decurcio for their noble work at ABO in Goiás. I would like to sincerely thank Rafael Araújo Câmara for his support. Thanks also go to my colleagues from SBOE and SBTI for all the knowledge I have received from you. I greatly respect these two associations. My greatest respect and gratitude goes to all those who have selflessly given their precious bodies to science. To my dear patients who allowed me to use their photos and clinical history to improve the knowledge of so many health professionals through this book, I cannot thank you enough. I would also like to acknowledge the important role of so many teachers I have had throughout my lifetime. I will always carry with me your teachings. Finally, my eternal gratitude to the greatest teacher of all, Jesus, for the daily blessings.

CHAPTER

01

Basic Principles of Botulinum Toxin

Botulinum toxin (BTX) is a biologic agent manufactured in a laboratory in the form of a crystalline stable substance, freeze-dried in human albumin, and supplied in a sterile, vacuum-dried vial to be reconstituted in a saline solution. It is naturally produced by Clostridium botulinum, a gram-positive anaerobic bacterium that produces several distinct serotypes of BTX (Box 1-1).1–3 In terms of cosmeceutical therapy, type A is the only one that shows a clinically important biologic activity, and hence it is the most often studied and used serotype of BTX.4 Type B is also commercially available to treat cervical dystonia and for patients resistant to BTX-A,5–8 but it is generally associated with a higher incidence of pain when injected and a short-lasting effect, although it has a faster onset than type A9–13 (Box 1-2).

Box 1-1 Serotypes of BTX

Box 1-2 Characteristics of BTX-A and BTX-B

BTX is an organic macromolecule made up of amino acids linked together by peptide bonds (polypeptide chains). Biochemically it consists of a 50-kDa light chain and a 100-kDa heavy chain (Fig 1-1) connected by protease-sensitive disulfide bridges; the bond of these chains results in a 150-kDa protein.14,15 This toxin is protected by larger nontoxic proteins and by hemagglutinin. The final weight of these multimeric complexes varies from 700 kDa for BTX-B to 900 kDa for BTX-A, reflecting the weight of the surface proteins that form such protection.1,2,16,17

Figure 1-2 illustrates a brief history of the discovery and scientific developments surrounding BTX.

Mechanism of Action of BTX

BTX-A should be injected in the muscle so that it disperses and diffuses to cholinergic nerve endings, where its mechanism of action takes place. BTX essentially breaks down fusion proteins (synaptosomal-associated protein 25 [SNAP-25]) responsible for the release of the neurotransmitter acetylcholine (ACh), thereby inhibiting muscle contraction in the fibers that receive the BTX injection.16–20 Figure 1-3 shows a detailed illustration of this process, as outlined below.

Once injected, BTX dissociates from the accessory proteins through the action of proteases. Immediately afterward, it is irreversibly bound to high-affinity specific receptors in the neuromuscular junction (NMJ). This is phase 1: binding.

Once the BTX molecule is bound to the receptor at the nerve cell membrane surface, the heavy chain allows the toxin to enter the cell through a membrane invagination, resulting in the formation of a vesicle that will surround the two chains of BTX. This process takes 20 minutes and is called receptor-mediated endocytosis. This is phase 2: internalization.

The light chain is then separated from the heavy chain by the dissociation of disulfide bridges through the action of proteases. Under an acidification condition, it is released from the vesicle to the neuronal cytoplasm. Once at the cytosol, the light chain performs its metalloproteinase activity at the intracellular targets that regulate the exocytosis of ACh vesicles. Such targets are part of the SNARE complex (soluble N-ethylmaleimide-sensitive factor attachment receptor) responsible for the binding and coupling of ACh vesicles. This complex is formed by the fusion of three proteins: SNAP-25, VAMP (vesicle-associated membrane protein), and syntaxin 1a.

The light chain of BTX-A, through a zinc-dependent endopeptidase and under an acidic pH, cleaves SNAP-25. (VAMP is cleaved by BTX-B, -D, and -F, and syntaxin 1a is cleaved by BTX-C.) This cleavage prevents the release of the neurotransmitter ACh. This is phase 3: blockage or proteolytic cleavage.

By inhibiting release of ACh from synaptic vesicles, BTX chemically denervates muscles and glands; this process is known as chemodenervation. This mechanism is specific to BTX-A and has wide clinical applications, including the modulation of muscle contraction, whose effect is clinically observed for 3 to 4 months. It may also be used to reduce hyperhidrosis for up to 12 months and excessive salivation for up to 6 months.

Action of BTX

The physiologic response to BTX injection is observed 6 hours after its administration, and clinical results are seen within 24 to 72 hours after the procedure.21 While clinical paralysis is observed 24 hours after the injection, the peak of the paralytic effect occurs 14 days later. Depending on individual factors such as doses and postblockage instructions, induced blockage by BTX can last from 2 weeks to 6 months22 (Box 1-3).

Box 1-3 Onset and duration of action of BTX

Once BTX is administered, the toxin response is irreversible during the period of time described above. However, eventually the effect is reversed. There are two hypotheses for the reversibility of the BTX effect:

1. Axonal sprouting and muscle reinnervation occur; that is, a new NMJ is formed.

2. Regeneration occurs at the same NMJ altered by the application of BTX. 23

Subsequently, new SNARE complexes form, thereby preventing the toxin from causing any other effect on the patient.

The duration of BTX-induced blockade, varying from weeks to months, vastly exceeds the recovery time of the action targets of the neurotoxin, which suggests that other intracellular actions are involved in the persistence of its effects. Furthermore, the duration as well as the blocking efficacy is dependent on the doses and formulations of the used serotypes.22 While the different biochemical cellular events that serve as a basis for this variance are unknown, many factors may contribute:

• Light chain lifetime inside the cytosol

• Turnover (protein renewal) of target SNARE proteins (VAMP, SNAP-25, and syntaxin 1a)

• Secondary biochemical events related to SNARE production and/or peptide release

The metabolic pathway has not been properly documented; however, it may be explained by the presence of proteases that lead to a degradation proteolysis of polypeptide chains present in the molecule.2

Biosafety

The toxin biosafety is evidenced by its selective action in the peripheral cholinergic nerve ending inhibiting ACh release. It does not pass the brain barrier or inhibit the release of ACh or any other neurotransmitter in this level. The toxin does not bind to nerve fibers of nerve stems or the postsynaptic region.2

Within the muscle, the amount of BTX administered is reduced to about half within approximately 10 hours. Within the 24 hours postinjection, 60% of the substance is excreted through urine.2

The Neuromuscular Histology

It is important to review the histology of muscle tissues before using BTX (Fig 1-4).

Characteristics of BTX-A

Box 1-4