Diagnosis and Treatment of Voice Disorders

Fourth Edition

John S. Rubin, MD, FACS, FRCSRobert T. Sataloff, MD, DMA, FACS

Gwen S. Korovin, MD, FACS

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Contents

Preface ixContributors xi

UNIT 1: BASIC SCIENCE 1

1 Formation of the Larynx: From Hox Genes to Critical Periods 3Jeffrey T. Laitman, Drew M. Noden, and Thomas R. Van De Water

2 Laryngeal Development 21David H. Henick

3 Anatomy of the Human Larynx 31Clarence T. Sasaki, Nwanmegha Young, Hiroumi Matsuzaki, and Boris Paskhover

4 Functional Fine Structures of the Human Vocal Fold Mucosa 49Kiminori Sato

5 The Microanatomy of the Vocal Fold Musculature 61Ira Sanders

6 Vocal Fold Extracellular Matrix and Wound Healing 79Marie E. Jetté and Susan L. Thibeault

7 Benign Vocal Fold Pathology Through the Eyes of the Laryngologist 95John S. Rubin and Eiji Yanagisawa

8 Laryngeal Function During Phonation 117Ronald C. Scherer

9 Laryngeal Neurophysiology 145Christy L. Ludlow

10 The Neurology of Stuttering 153Savita Kumari, Rebecca Spain, Steven Mandel, and Robert T. Sataloff

11 Toward a Dynamical Diagnosis of Vocal Function 165R. J. Baken and Robert F. Orlikoff

12 Research in Laryngology 177Gayle E. Woodson

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UNIT 2: CLINICAL ASSESSMENT 183

13 Patient History 185Robert T. Sataloff

14 Physical Examination 211Robert T. Sataloff

15 Evaluation of Laryngeal Biomechanics by Transnasal Flexible Laryngoscopy 223Jamie A. Koufman

16 Transnasal Esophagoscopy 235Nancy L. Solowski and Gregory N. Postma

17 Introduction to the Laboratory Diagnosis of Vocal Disorders 245Gwen S. Korovin, John S. Rubin, and Owain R. Hughes

18 Measuring Vocal Fold Function 253Raymond H. Colton and Peak Woo

19 Laryngeal Electromyography 289Elizabeth Guardiani, Babak Sadoughi, Lucian Sulica, Tanya K. Meyer, and Andrew Blitzer

20 Videography and Photography of the Larynx 303Eiji Yanagisawa, Ken Yanagisawa, and H. Steven Sims

21 3D Laryngeal CT Scan for Voice Disorders: Virtual Endoscopy — Virtual Dissection 321Jean Abitbol, Albert Castro, Rodolphe Gombergh, and Patrick Abitbol

22 The Evaluation of Voice Outcomes and Quality of Life 347Michael S. Benninger and Glendon M. Gardner

23 Voice Impairment, Disability, Handicap, and Medical/Legal Evaluation 357Robert T. Sataloff

UNIT 3: MANAGEMENT 369

24 Common Medical Diagnoses and Treatments in Patients With Voice Disorders 371Robert T. Sataloff and Mary J. Hawkshaw

25 Congenital Anomalies of the Larynx 389Ted L. Tewfik, Steven E. Sobol, and Alyssa A. Kanaan

26 Pediatric Laryngology: Office-Based Evaluation of Children With Dysphonia 411Jennifer Setlur and Christopher J. Hartnick

27 The Older Voice 421Robert T. Sataloff

ContEnts vii

28 The Larynx: A Hormonal Target 431Jean Abitbol and Patrick Abitbol

29 Laryngopharyngeal Reflux and Voice Disorders 457Jamie A. Koufman

30 Infectious and Inflammatory Disorders of the Larynx 471Catherine F. Sinclair and Robert S. Lebovics

31 Cough and the Unified Airway 489Rupali N. Shah and Kenneth W. Altman

32 Neurologic Disorders and the Voice 501Marshall E. Smith and Lorraine Olson Ramig

33 Unilateral Vocal Fold Paralysis 527Michael S. Benninger and Glendon M. Gardner

34 Bilateral Vocal Fold Paralysis 549Michael S. Benninger and Glendon M. Gardner

35 Management of the Spasmodic Dysphonias 563Joel H. Blumin and Christy L. Ludlow

36 Psychologic Aspects of Voice Disorders 587Deborah Caputo Rosen, Reinhardt J. Heuer, David A. Sasso, and Robert T. Sataloff

37 The Voice and Medications 617Thomas M. Harris, Harsha H. Kariyawasam, and John S. Rubin

38 Corticosteroid Therapy in Otorhinolaryngology 631Harsha H. Kariyawasam, Simon K.W. Lloyd, Giuseppina Rotiroti, and John S. Rubin

39 The Role of the Speech-Language Pathologist in the Treatment of Voice Disorders 645Thomas Murry and Clark A. Rosen

40 The Role of the Voice Specialist in the Nonmedical Management of Benign 659 Voice DisordersLinda M. Carroll

41 The Role of the Voice Coach in the Treatment of Vocal Disorders 683Barbara Houseman

42 The Effects of Posture on Voice 707Lesley Mathieson, John S. Rubin, and Ed Blake

43 Special Considerations for the Professional Voice User 719John S. Rubin, Gwen S. Korovin, and Ruth Epstein

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44 Occupational Voice 735Orietta Calcinoni and Ewa Niebudek-Bogusz

45 Anesthesia in Laryngology 763Anil Patel and John S. Rubin

46 Laryngotracheal Trauma 771Yolanda D. Heman-Ackah

47 Surgical Management of Benign Voice Disorders 789Mark S. Courey, Daniel S. Fink, and Robert H. Ossoff

48 Adult-Acquired Laryngotracheal Stenosis 813Guri S. Sandhu and David J. Howard

49 Vocal Fold Medialization: Injection and Laryngeal Framework Surgery 833Steven M. Zeitels

50 Laryngeal Reinnervation: Traditional Approaches 847Harvey M. Tucker

51 Reinnervation: New Frontiers 855Jean-Paul Marie

52 Emerging Approaches to Laryngeal Replacement and Reconstruction 871Jonathan M. Fishman, Paolo De Coppi, and Martin A. Birchall

53 Recurrent Respiratory Papillomatosis 887Craig S. Derkay and Salvatore Taliercio

54 Premalignant Lesions of the Larynx 905Amanda Hu, Carole M. Dean, and Robert T. Sataloff

55 Glottic Carcinoma: Disease Presentation and Philosophy of Management 921Steven M. Zeitels

56 Diagnosis and Management of Postoperative Dysphonia 951Peak Woo

57 Office-Based Phonosurgery 969Markus M. Hess and Susanne Fleischer

58 Telemedicine 981John S. Rubin and Robert T. Sataloff

Index 985

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Preface

It has been almost 10 years since publication of the third edition of Diagnosis and Treatment of Voice Disor-ders. This past decade has heralded in a new digital age, the likely eponym for the subsequent half cen-tury. There has been a veritable explosion of advances based on the associated sharing of information, and these advances have informed practically every aspect of voice care, from the bench to the operating table.

Wilbur James Gould, mentor and dear friend of each of the editors, foresaw the benefits of information sharing, its implicit role in scientific advancements to voice care, and the crucial role of such a multidisci-plinary approach to patient welfare. We once again dedicate this fourth edition to Dr Gould and rededi-cate ourselves to his vision.

The fourth edition now has 58 chapters (compared with 48 in the third edition). It is subdivided into units: Basic Science (Chapters 1–12), Clinical Assessment (Chapters 13–23), and Management (Chapters 24–58). In preparing the fourth edition, we have endeavored to retain the format of the previous three editions but at the same time to incorporate new materials in a reader-friendly manner. To that end, a few chapters have needed minimal to no revision, some chapters have undergone extensive updates or have been rewritten completely, and some chapters have been divided into two to present the new materials better. There also have been a number of chapters written by new authors and chapters written on new subjects specifically for this edition.

Examples of chapters that are classics and required little to no rewriting include David Henick’s chap-ter “Laryngeal Development,” Ira Sander’s chapter “Microanatomy of the Vocal Fold Musculature,” and Jean and Patrick Abitbol’s chapter “The Larynx: A Hor-monal Target.”

Chapters with extensive updates to keep pace with changes in knowledge include Jeffrey Laitman and colleagues’ chapter “Formation of the Larynx: From Hox Genes to Critical Periods” and Kiminori Sato’s chapter “Functional Fine Structures of the Human Vocal Fold Mucosa.” Not surprisingly, expansion of information about the genome has led to better under-

standing of formative stages of embryogenesis; such information is now also becoming applicable to the structures of the vocal fold mucosa.

Examples of chapters with shifts in focus expressed through their revisions/rewrites include Ronald Baken and Robert Orlikoff’s chapter “Toward a Dynamical Diagnosis of Vocal Function,” Jamie Koufman’s chapter “Laryngopharyngeal Reflux and Voice Disorders,” and Steven Zeitels’s “Glottic Carcinoma: Disease Presentation and Philosophy of Management.” In these chapters, the authors show substantial changes in their approach to or under-standing of the problem. For example, Ronald Baken and Robert Orlikoff postulate use of nonlinear vocal behavior models for diagnosis of discrete laryngeal pathology, Jamie Koufman approaches laryngopha-ryngeal reflux from a position akin to oncology, and Steven Zeitels reports on adjuvant therapies not even considered in the third edition.

In this edition, we have not only requested new authors for selected previous chapters but also expanded the book with a number of chapters on entirely new subjects. These additions are found in each section of the book. Some of the additions are paired with previous chapters, such as Jean-Paul Marie’s chapter “Reinnervation: New Frontiers,” paired with Harvey Tucker’s chapter “Laryngeal Reinnervation: Traditional Approaches,” and Barbara Houseman’s chapter “The Role of the Voice Coach in the Treatment of Voice Disorders,” paired with Linda Carroll’s chap-ter “The Role of the Voice Specialist in the Nonmedical Management of Benign Voice Disorders.” Some of the additions present new trends in clinical management such as Markus Hess and Susanne Fleischer’s chapter “Office-Based Phonosurgery,” Nancy Solowski and Gregory Postma’s chapter “Transnasal Esophagos-copy,” and Rupali Shah and Kenneth Altman’s chapter “Cough and the Unified Airway.” Particularly in the clinical chapters, evidence-based and clinical-based research is matched with step-by-step protocols and methods to avoid pitfalls.

Some of the new chapters offer insights and ideas not readily available at the time of the previous

x diagnosis and trEatmEnt oF VoiCE disordErs

edition. Examples might include John Rubin and Robert Sataloff’s chapter “Telemedicine” or Orietta Calcinoni and Ewa Niebudek-Bogusz’ chapter “Occu-pational Voice.” We believe that some of the chapters will actually appear to the reader to be substantially ahead of the current time or at the very cutting edge. Examples might include Jonathan Fishman and col-leagues’ chapter “Emerging Approaches to Laryngeal Replacement and Reconstruction,” Marie Jetté and Susan Thibeault’s chapter “Vocal Fold Extracellular Matrix and Wound Healing,” and Christie Ludlow’s chapter “Laryngeal Neurophysiology.”

In summary, this fourth edition of Diagnosis and Treatment of Voice Disorders provides a vibrant, up-to-date, accessible, and clear reference for the various

professionals entrusted with the care of patients with voice disorders, be they laryngologists or phoniatri-cians, speech-language pathologists or logopeds, physical therapists, osteopaths or other practitioners of complementary medicine, singing or acting voice specialists, acoustic or voice scientists, psychiatrists or psychologists, gastroenterologists, pulmonologists, or neurologists, nurses, or other allied medical spe-cialists. It is written in language intended to be acces-sible to an interdisciplinary readership, and we hope that the information presented will prove not only useful but also inspirational to all voice care profes-sionals since each of us has the opportunity to add new knowledge to this exciting and rapidly advanc-ing field.

— John S. Rubin Robert T. Sataloff Gwen S. Korovin

Unit 1Basic science

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1Formation of the Larynx:

From Hox Genes to Critical Periods

Jeffrey T. Laitman Drew M. Noden

Thomas R. Van De Water

The human larynx is a compact and complex struc-ture that must serve respiratory, protective, and vocal-ization functions. Although there have been several descriptions of the major histogenic and morphogenic events during laryngeal development in humans1 and other mammals,2 only recently have accurate fate map-ping and molecular expression data become available.

The larynx arises at the interface of “head” and “trunk” regions of the embryo, and cells from both sides of this interface move to the site of laryngeal development. Also, it is the only musculoskeletal assembly intimately associated with the endodermal gut tube. These unique attributes make dissecting the cellular and molecular basis of laryngeal develop-ment especially difficult and, to date, neglected.

This chapter addresses two aspects of laryngeal development that are especially critical to under-standing the structure-function relations both within

this complex and between it and adjacent structures. First, we review early embryologic events and pro-cesses, including the genesis of laryngeal tissues and interactions, both cellular and genetic, which are essential for the normal histogenesis and morpho-genesis of the larynx. Second, we identify and discuss significant critical periods in prenatal and postnatal laryngeal development in humans.

ESTABLISHING LARYNGEAL PRIMORDIA

Common Developmental Themes

Laryngeal development requires the determination and integrated movements of several cell lineages that converge beside the caudal aspect of the pharynx.

4 diagnosis and trEatmEnt oF VoiCE disordErs

These epithelial and mesenchymal precursors of mucosa, loose and dense connective tissues, volun-tary and smooth muscles, blood vessels, and nerves have greatly varied embryonic histories, and each cell lineage undergoes developmental programming that prepares its members to participate as chondro-cytes, myocytes, and other components of laryngeal morphogenesis.

Achieving this programming requires a progres-sive series of interactions involving other cells and the extracellular milieu that alter the function of specific genes, which in turn changes the response character-istics of cells to subsequent interactions. These inter-actions affect rates of cell proliferation, pathways and speeds of cell migration, and both the commitment to and the expression of specific cell phenotypes. Clearly, such processes must be temporally and spatially coor-dinated in order for so many disparate progenitors to achieve an integrated outcome.

A multicomponent musculoskeletal laryngeal apparatus is absent in anamniotes, although some ter-restrial amphibians do have cartilaginous rods that partially circumscribe an elongated glottis. This single skeletal element is often cited as being an anteced-ent to at least one of the laryngeal skeletal elements and is thought to have evolved from gill-associated cartilages. However, there is little direct evidence for either of these claims. However, among amniotes, many laryngeal precursor populations have sites of origin that are evolutionarily conserved. A key feature of this conserved plan is the presence in all vertebrate embryos of a segmental organization within many tis-sues that are developmentally related to the larynx. This is manifest especially in hindbrain, branchial arch, and trunk axial regions. Although the larynx is not generally viewed as a segmentally organized set of structures, tissues developing nearby, many formed from common progenitors, do exhibit a meta-meric organization during their development. And immediately caudal to the larynx, the tracheal rings present a metameric pattern.

The expression patterns of several members of gene families that are involved in lineage delineation and spatial programming of head and neck tissues similarly show a segmental organization. Abnormal expression of some of these genes, either as a result of germ line mutations in humans or experimental gene manipulation in transgenic mice, also results in dis-ruptions of hindbrain, branchial, otic, and laryngeal morphogenesis.

The first objective of this section is to identify the origins of laryngeal precursors and document their movements to the site of laryngeal morphogenesis. The second goal is to identify when and where each

of these populations become programmed to form tis-sues of the types and shapes appropriate to their final location, including the genetic bases for their decisions. The reader should be warned that laryngeal develop-ment has received little attention by experimental biologists. Thus, some hypotheses regarding laryngeal development presented here are by inference, based on properties of neighboring structures and experi-mental analyses in only a few model systems.

Origins of Laryngeal Precursors

Overview

The epithelial lining of the larynx forms close to the caudal margin of the embryonic pharynx, although this site is otherwise indistinct from the adjacent parts of the primitive endodermal tube. Rostral to this site, the pharynx forms a set of segmentally arranged, lateral endodermal outpocketings, the pha-ryngeal pouches, between which are located the bran-chial arches (also referred to as pharyngeal or visceral arches). Present within each branchial arch are pre-cursor populations for connective tissues, skeletal muscle, blood vessels, and peripheral neurons. These may be segregated from their neighbors (eg, skeletal myoblasts) or fully interspersed (eg, endothelial pre-cursors). Some vertebrates establish a large number of branchial arches, retaining many as gills, but amni-otes (reptiles, birds, and mammals) form only 3 or 4 recognizable branchial arch swellings on each side of the head (Figure 1–1). True fifth and sixth branchial arches do not form in amniotes.

During the neurula stage, embryos establish sets of structures common to all developing vertebrates. The neural tube is located dorsally (posteriorly) and is flanked on each side by paraxial mesoderm. Along most of the body length, this mesoderm forms cuboi-dal epithelial blocks called somites. In the head, how-ever, paraxial mesoderm fails to epithelialize and does not display an overt segmental organization. Ventrally, the endodermal sheet folds to form a gut tube, consisting of the pharynx, rostrally, that is con-tinuous with the future fore-, mid-, and hind-gut pas-sageways. When first formed, this endodermal tube is enveloped laterally and ventrally by lateral mesoderm. This sparse mesoderm becomes partially displaced by a secondary population of mesenchymal cells, the neural crest.

The neural crest brings a new population of con-nective tissue precursors to parts of the head in all vertebrates. Crest cells arise from the roof of the brain or neural folds and move en masse to fill the areas between each pharyngeal pouch and also circum-

Formation oF thE Larynx: From Hox gEnEs to CritiCaL PEriods 5

scribe the prosencephalon (Figure 1–2). The hind-brain, from which the majority of branchial arch crest cells originate, is a segmentally organized tubular structure, and the crest cells that enter each branchial arch can be traced to specific segments.

Connective tissues of the larynx develop at the boundary of tissues derived from the neural crest and those derived from lateral mesoderm. Caudal (poste-rior) to this, all connective tissues associated with the endodermal tube — including tracheal rings — are of lateral mesoderm origin.

The preceding overview highlights the complex-ity of laryngeal embryology owing in large part to its association with the ventral endodermal tube and location at the head-trunk interface. The following sections provide detailed accounts of each component of the developing larynx.

The Respiratory Diverticulum

The epithelial lining of the pharynx, from which the respiratory diverticulum arises, is formed along with the endodermal lining of the pharynx and gut dur-

ing early gastrulation stages. Cells within the epiblast, which is the superficial layer of the embryonic disc (inner cell mass), move internally beginning at the junction of the epiblast and early primitive streak: these establish a new, internal epithelial layer, the endoderm.3 Once internalized, the endodermal sheet expands rapidly and forms the entire intraembryonic endodermal primordium. Shortly thereafter, the posi-tional identities of most endodermal structures (eg, thyroid, thymus, stomach, pancreas) become specified.

Endodermal cells that will give rise to laryngeal mucosa are initially located beneath (ventral to) the future postotic hindbrain region. Analyses of dice-phalic neonates reveal that only when the site of skull duplication occurs as far caudally as the occipito- atlanto-axial region, which flanks the caudal hindbrain, will there also be paired larynges. Duplications that extend only to the spheno-occipital (mid-hindbrain) level will have a single laryngeal apparatus.

The respiratory diverticulum (laryngotrachial groove, tracheal diverticulum) is first evident as a ventrally expanded trough projecting from the floor of the pharynx beginning at the level of the fourth (most

Figure 1–1. scanning electron micrograph showing the swellings of the first (1), second (2), and third (3) branchial (pharyngeal) arches, which have formed by the movement of neural crest cells from dorsal, neural to ventral, pharyngeal regions. the grooves between each arch represent the sites of apposition between surface ectoderm and underlying pharyngeal pouches. note the location of the prominent heart primordium, which at this stage has already begun to loop. the heart will subsequently shift its position caudally as the branchial arches and caudal pharyngeal region remodel. about 14 somites are visible; * indicates somite 1. the specimen is a 16-day, 22-somite domestic cat embryo, which corresponds to a stage 12 (30-day) human embryo.

6 diagnosis and trEatmEnt oF VoiCE disordErs

caudal) pharyngeal pouch.1 Shortly after this evagi-nation forms, distinct lateral outpocketings emerge bilaterally from the caudal margin of this trough; these demarcate the future bronchial-pulmonary structures. Partial separation of the ventral (respiratory) from dorsal (esophageal) regions of the caudal pharynx occurs by a caudal-to-cranial dying off of intermedi-ate endodermal epithelial cells.4,5 This is followed by a rapid caudal elongation of both the respiratory diver-ticulum and the esophagus.6,7 Subsequent stages in the development of the respiratory diverticulum are presented in greater detail in Chapter 2.

It is not known how the precise site at which the respiratory diverticulum forms is specified. Similar to several other endoderm-derived structures (eg, the thyroid and pancreas), the early histogenic remodel-

ing of the respiratory diverticulum requires the pres-ence of a cholesterol-associated growth factor called sonic hedgehog.8 Reducing the level of sonic hedgehog biosynthesis by cells of the respiratory diverticulum, or disabling the ability of adjacent mesoderm cells to properly respond, results in defects of tracheoesopha-geal separation and tracheal chondrogenesis.9 These dysmorphologies can be isolated, but in humans are more commonly syndromic (eg, Pallister-Hall, Smith-Lemli-Opitz, and VACTERL syndromes).10,11

Lateral Mesoderm

The onset of intraembryonic mesoderm formation fol-lows the appearance of endoderm, but this mesenchy-mal population rapidly expands to fully overlie the

Figure 1–2. transverse sections of chick embryos stained with an antibody to neural crest cells. A shows a 12-somite embryo at the level of the otic placode (inner ear primordium). Crest cells have recently emerged from the roof of the hindbrain. B is at the preotic (rhombo-mere 4), first pharyngeal pouch region of a 16-somite chick embryo; note the sharp boundary between crest and underlying paraxial mesoderm. C is a 25-somite embryo. by this stage, crest cells have completed their ventral movements and, after the outflow tract of the heart (o.t.) shifts caudally, will join in the midline to complete the formation of the lower jaw region. unla-beled cells within the branchial arch are mesodermal cells that will form the jaw musculature.

Formation oF thE Larynx: From Hox gEnEs to CritiCaL PEriods 7

endodermal sheet. In human embryos, this process is complete by the end of the second week of gestation, and spatial relations established at these early stages remain constant throughout subsequent stages.

Fate mapping studies in avian embryos have iden-tified lateral mesoderm located beside the first and second somites as the source of the arytenoid and cri-coid cartilages (Figure 1–3A).6 These data contradict previous assertions, based on descriptive studies, that all skeletal elements associated with the larynx are homologous to gill-associated skeletal structures in anamniotes and as such would be derived from bran-chial arch neural crest cells. Birds do not have struc-tures homologous to thyroid and epiglottis cartilages, and thus the embryonic origin of this element could not be determined from these avian studies.

Lateral mesoderm located caudal to the laryngeal primordium forms the tracheal cartilages and associ-ated connective tissues. Analyses of expression pat-

terns of early chondrogenic genes such as sox9 and collagen 2A1 reveal that tracheal cartilage precursors are initially specified as a continuous longitudinal band within mesoderm located dorsolateral to the proximal (cranial) half of the respiratory diverticu-lum.12 Later, this band becomes subdivided into dis-crete, regularly spaced chondrogenic foci, each of which subsequently expands ventrally.

A detailed molecular biography of laryngeal chondrogenesis is not yet available. Human patients and transgenic mice with haploinsufficiency of sox9 expression have, among other skeletal defects, upper airway defects secondary to hypoplasia of laryngeal and tracheal cartilages.13

Lateral mesoderm located rostral to the laryngeal primordium is exclusively angiogenic and cardio-genic. Embryonic angioblasts are one of the earliest progenitor populations to be delineated and consti-tute more than one-third of the early mesodermal

Figure 1–3. origins of laryngeal cartilages and intrinsic muscles. A shows a transverse sec-tion of the larynx from a chick embryo that received a transplant of quail lateral mesoderm at an earlier stage. Quail cells are identified in the left arytenoid cartilage by their prominent dense nuclear marker, which is not present in chick tissues. B is from a chimeric embryo in which quail paraxial mesoderm cells were grafted. this section shows quail cells (arrows) contributing to an intrinsic laryngeal muscle, the dilator glottidis, but not to associated con-nective tissues. C shows the laryngeal cartilages, dissected apart for clarity, from a neonatal mouse in which all cells derived from the neural crest contain a reporter gene construct (labeled blue). the epiglottis and thyroid cartilages are derived from the neural crest; the other laryngeal cartilages are mesodermal in origin. Sources: a. noden51; b. noden.18