EXPERIMENTAL STUDIESILSA SCHWARTZ, PhDExperimental Study Editor

Bilateral thyroarytenoid denervation:a new treatment for laryngeal hyperadductiondisorders studied in the canineJOEl A. SERCARZ, MD,GERALD S. BERKE, MD,YE MING, MD,JAMES ROTHSCHILLER, MD,and

MICHAEl C. GRAVES, MD,Los Angeles, California

Adductor spasmodic dysphonia is a vocal disorder of uncertain etiology with no sat­isfactory long-term treatment. Recently, injection ot botulinum toxin (Botox) into thethyroarytenoid (TA) muscle has been used as an effective temporary treatment. Asurgical counterpart to bilateral TABotox injection is described in this article. Bilateralthyroarytenoid denervation was performed through a window in the thyroid cartilagein seven canines, including four that were studied 3 months after the procedure. Noserious complications occurred in the animals, each maintaining full vocal fold ab­duction and adduction. In all cases, anticipated physiologic changes in laryngealfunction were observed, including the inability to generate high subglottic pressuresduring high levels of laryngeal nerve (RLN) stimulation. In two of the surviving animals,the ansa cervicalis was used to reinnervate the TA muscle, thereby preventing thepossibility of reinnervation from the proximal RLN stump while limiting TA atrophy andfibrosis. Bilateral TAdenervation represents a hopeful new long-term approach to spas­modic dysphonia treatment. (OTOLARYNGOL HEAD NECK SURG 1992;107:657,)

Adductor spasmodic dysphonia (ASD) is a heterog­enous vocal disorder of uncertain etiology resulting ina halting, staccato, strained vocal pattern. The diseasehas frustrated laryngologists because of the lack of ef­fective long-term treatment.

This study proposes a new operation for ASD relyingon accumulated experience with previous medical andsurgical treatments. In the procedure, a small windowin the thyroid cartilage was used to gain access to theintralaryngeal recurrent laryngeal nerve (RLN) in orderto selectively denervate the thyroarytenoid muscle (in­cluding the medial or vocalis fibers). When performedbilaterally, the procedure has theoretical justification inthe treatment of ASD. An in vivo canine model ofphonation served to verify the anatomic and technical

From the UCLA School of Medicine Division of Head and NeckSurgery. (Drs. Sercarz, Berke. and Rothschiller) and the EMGLaboratory .

Supported by V.A. Merit Review Research Fund.Presented at the Annual Meeting of the American Academy of Oto­

laryngology-Head and Neck Surgery, Kansas City. Mo., Sept. 22­26, 1991.

23/10/40954

aspects of the procedure and to document the physio­logic changes produced.

The etiology of spasmodic dysphonia is unknown.Evidence has accumulated that contradicts the initialstudies indicating that ASD is a psychiatric illness. Re­search has uncovered several neurologic abnormalitiesin ASD patients. Schaefer found impairment in somaticand visceral brainstem pathways in spasmodic dys­phonic patients. 1 Davis et al. 2 found neurologic defectsin eight of 13 patients with ASD. Although each patienthad a clinical diagnosis of ASD, there were significantdifferences among the subjects in phonatory airflow,fundamental frequency, and laryngeal appearance dur­ing phonation. Davis et al. 2 concluded that ASD mayrepresent a physiologically diverse group of patients.The clinical diversity observed in ASD patients sug­gests a complex etiology, possibly involving the inter­play of psychiatric and neurologic factors. 2

This interplay may explain why the treatment of spas­modic dysphonia based upon the premise that it is pri­marily a psychiatric disorder has been unsuccessful.Speech therapy has likewise been unsuccessful as a soletherapy for ASD. While behavioral treatments for ASDare abundant, most behaviorists admit that they are

657

658 SERCARZ et 01.

PosteriorCricoarytenoidMU..!lcle

Ololaryngology­Head and Neck Surgery

Fig. 1. RLN branching in the human being based upon cadaver dissection. The thyroid cartilage iscut vertically and retracted. The window for access to the terminal RLN is included.

successful in treating only a subgroup of the disorder.Because ASD is a heterogeneous disorder, a trial ofspeech therapy may be beneficial in some patients, par­ticularly those with mild symptoms.

Nonbehavioral treatments aimed at preventing thespastic hyperadduction of the vocal folds can be clas­sified into: (1) surgical deinnervation of the recurrentlaryngeal nerve (RLN) trunk, (2) injection of botulinumtoxin directly into the TAmuscle, and (3) phonosurgica1techniques. Initially quite promising, surgical treat­ments for the disease such as RLN section have notproved long-lived. 3

Ded04 presented the first data on the use of RLNsection for ASD in 1976. In theory, the creation of aunilaterally paralyzed larynx would prevent vocal fold

hyperadduction. However, this benefit was at the pos­sible cost of a breathy voice and the other sequelae ofunilateral vocal paralysis. Dedo and Izdebski" subse­quently developed the widest experience with RLN sec­tion, and in 1983 reported intermediate followup on306 patients. Surgical outcome was evaluated primarilyby self-assessment. Their study found recurrent spas­ticity in only 10% to 15% of patients. Ninety percentof their patients reportedly termed the operation satis­factory and would recommend RLN section to otherswith spasmodic dysphonia."

In an effort to be more objective, Aronson et al.3

used clinician experts to assess the results of RLN sec­tion. In their study of 33 patients treated with RLNsection, 97% of patients showed improvement in voice

Volume 107 Number 5November 1992

1 month after surgery. When the same patients werefollowed for 3 years, however, only 36% were stilljudged to be improved."

Despite the patients' willingness to believe it helped,failure of RLN section to provide long-term relief ofdysphonia was thought to be related to the persistentspasticity in the remaining innervated hemilarynx.However, reinnervation by proximal RLN axon re­growth has also been reported on the basis of EMGdata."

In contrast to the high surgical failure rate, Blitzeret al.7 in 1986 reported positive early experience withbotulinum toxin (Botox) for spasmodic dysphonia. Lo­cal injections of botulinum toxin had been used pre­viously to treat blepharospasm, torticolis, and hemi­facial spasm. The goal of treatment was to createneuromuscular blockade of the TA muscle. Electro­myographic (EMG) recordings made after administra­tion of Botox verified the denervation of the TA.8 Al­though an important advance, many laryngologistsagree that Botox probably is not the ultimate solutionto ASD. One drawback of Botox is that the treatmentsare temporary and may require reinjection every 3 to 6months. The long-term results and safety of Botox in­jection are unknown. Blocking antibodies have beenreported in the serum of patients undergoing Botoxtherapy. In some cases, a breathy voice or vocal cordparalysis occurs as a complication of the injection. Fi­nally, the dose response curve of Botox can vary greatlybetween individuals.

This study reports on the use of bilateral selectiveTA denervation in the canine model of phonation. Bi­lateral TA denervation is a permanent surgical analogfor the temporary effects of bilateral TA Botox injec­tion. Because the procedure had not been tried in humanbeings bilaterally, it was performed and evaluated usingan in vivo canine model of phonation.

Phonosurgery is now a well-accepted method of al­tering the laryngeal framework to alter phonation. Thisstudy proposes an intralaryngeal modification in anattempt to achieve a specific functional goal.

METHODS AND MATERIAL

Readers interested in a detailed explanation of the invivo model of phonation with physiologic implicationsare referred to previous studies from our laboratory. 9.10

Anatomic Study

Three canine and five human larynges were harvestedfresh. The recurrent laryngeal nerve was identified inthe neck and followed to its laryngeal entrance adjacent

Bilateral thyroarytenoid denervation 659

Fig. 2. A, Window in the thyroid cartilage in human cadavericspecimen. B, Careful dissection in the plane medial to theinner thyroid perichondrium provides access to the distai RLNbranch destined for the TA muscle, as seen traversing thewindow.

to the cricothyroid articulation. On its entrance into thelarynx, the RLN courses lateral to the PCA muscle,giving off a small posterior division. The anterior di­vision courses anterosuperiorly just deep to the innerperichondrium lateral to the lateral cricoarytenoid(LCA) muscle, terminating in the TA muscle. The an­terior division supplies the interarytenoid, lateral cri­coarytenoid, and thyroarytenoid/vocalis muscles. Fig­ure 1 depicts a typical branching pattern from a humancadaver in relation to the laryngeal framework, consis­tent with previous descriptions. 11

The terminal RLN branching pattern is similar incanine and human larynges. The anterior division ofthe RLN can be accessed through a small inferiorlybased thyroid cartilage flap, as illustrated in a humancadaver larynx in Fig. 2, A and B.

Visually, the nerve can be followed anterosuperiorlyto its terminus, most often in the shape of a fan spread­ing into the fibers of the TA. l l If identified in this fash-

660 SERCARZ et 01.

PGGPROCESSOR

..

t

t

..

Otolaryngology­Head and Neck Surgery

MULTICHANNELSTORAGE

OSILLOSCOPE

DIRECTCOMPUTERIZEDDIGITIZATION

FLOWMETER

tH••I.llft.d.arm air

V••tll.tor

Fig. 3. Schematic representation of the experimental set-up for the in vivo canine model of pho­nation.

ion, the nerve can be reliably sectioned distal to theLeA branch.

In Vivo Preparation: Acute Studies

On the basis of the anatomic study indicating thefeasibility of approaching the distal RLN through athyroid cartilage window, physiologic data were ob­tained in three live canine subjects. In all cases, bilateraldenervation of the terminal branch of the recurrent la­ryngeal nerve was performed. Animals were studiedbefore and subsequent to denervation using an in vivocanine model of phonation. Dependent measures, in­cluding glottographic and subglottic pressure signals aswell as videostroboscopic images, were obtained. A

diagram depicting features of the in vivo canine modelof phonation is shown in Fig. 3.

The animals were premedicated with acepromazineintramuscularly and given intravenous pentothal titratedto achieve corneal anesthesia throughout the procedure.

A midline incision was made to expose the tracheafrom the hyoid bone to the sternal notch. The strapmuscles were divided bluntly in the midline and re­tracted laterally. The external branches of the superiorlaryngeal nerve were exposed bilaterally and their iden­tity was verified with a nerve stimulator. Harvard bi­polar electrodes were applied to the nerves. The re­current laryngeal nerves were isolated 5 ern inferior tothe larynx, and bipolar electrodes were applied. A plas-

Volume 107 Number 5November 1992

tic button sutured through the thyrohyoid membranewas used to suspend the epiglottis anteriorly.

A distal tracheostomy was performed and the animalwas ventilated with oxygen supplied by a mechanicalventilator. A proximal tracheostomy was performedthrough which a cuffed endotracheal tube was placed,with its tip resting 10 cm below the glottis. The cuffof the superiorly placed tracheostomy was filled tojust seal the trachea. Room air was bubbled through 5cm of water at 37° C for warming and humidifica­tion and passed through the cephalad tracheostomytube.

A photosensor (Centronics OSD 50-2, Mountainside,N.J.) was placed on the animal's trachea, approxi­mately 3 ern below the larynx. A halogen flashlightprovided supraglottic illumination for photoglottogra­phy (PGG). Electroglottographic (EGG) signals wereobtained with a laryngograph (Synchrovoice, Harrison,N.J.) with the two recording electrodes placed in pock­ets just above the cricothyroid muscles adjacent to thethyroid cartilage (Fig. 3).

A microphone (Sennheiser, Old Lyme, Conn.) wasplaced 15 ern from the vocal folds and connected to aModel 8000 laryngostroboscope (Karl Storz, CulverCity, Calif.) for frequency analysis of the induced pho­nation. The stroboscope source was connected with atiberoptic cable to a O-degree Karl Storz telescope forobservation of vocal fold vibration.

A catheter-tipped pressure transducer (Millar modelno. SPC 330, Houston, Texas), inserted through theupper tracheotomy, rested 2 em below the glottis. Thetransducer was calibrated at the temperature of the an­imal's trachea by submerging the transducer in a waterbath at 37° C to a depth just covering the sensor (0.5cm) and then calibrating it against a manometer fromo to 120 cm H20 .

Phonation was induced by insufflating air past thevocal folds at a flow rate of 318 cc / sec during electricalstimulation of the recurrent and superior laryngealnerves (SLN). SLN stimulation was held constant at0.1 volt to produce moderate contraction of the crico­thyroid muscle. RLN stimulation was varied from 0 to15 milliamps.

Videostroboscopy was performed during simulatedphonation with 0.4 V SLN stimulation and 0.6 milliampRLN stimulation and an airflow of 318 cc/sec. Theimage was detected by a Jed-Med CCD video camera(model 70-5110) and a Sony U-matic videocassette re­corder (VO-5850).

During phonation, EGG, PGG, and subglottic pres­sure signals were low-pass filtered at 3 kHz, then dig-

Bilateral thyroarytenoid cenervofton 661

itized at 20 kHz and stored in a personal computer. Thewaveforms were analyzed using a commercially avail­able software package for the PC system (C-Speech,Paul Milenkovic, University of Wisconsin, Madison,Wis.). At least three trials before and after bilateral TAdenervation were digitized for each animal.

Surgical Denervatlon Procedure

The strap muscles were retracted laterally for accessto the larynx. The inferior constrictor muscle was di­vided and retracted to expose the thyroid cartilage. Awindow (approximately 8 x 12 mm) was made in thethyroid lamina as an inferiorly based cartilaginous flap(Fig. 2). The flap was designed so that it extendedinferiorly to the uppermost cricothyroid muscle fibers.The inner perichondrium was incised and the intralar­yngeal musculature was gently dissected using a he­mostat. The TA branch of the RLN was easily identifiedin all animals lateral to the TA muscle intraiaryngeally.Positive identification of the terminal branch was ver­ified by 0.2 milliamp DC stimulation producing vocalisbulging without vocal cord adduction. Sectioning of theTA branch of the RLN was performed anterosuperiorto the LCA muscle to avoid the possibility of LCAdenervation.

In Vivo Preparation: Chronic Studies

An additional four animals were studied 4 monthsafter bilateral TA branch denervation. For the study,adult canines (>25 kilograms each) were premedicatedwith acepromazine intramuscularly. Fluorane anesthe­sia, delivered by means of an endotracheal tube, wasused during the procedures. The denervation procedurewas performed as previously described.

In two of the chronic animals (animals 1 and 2),denervation was performed by locating the TA branchof the RLN, resecting a 5 mm segment, and cauterizingthe proximal cut end to prevent reinnervation. The othertwo surviving canines (animals 3 and 4) underwentsurgical reinnervation of the distal (TA) branch of theRLN with an appropriately sized ipsilateral ansa cer­vicalis branch. The reinnervation scheme is depicted inFig. 4 using a human larynx as an example. Standardmicrosurgical techniques and 10-0 nylon suture wereused for the nerve anastomoses. The thyroid cartilageflap was replaced and closed using absorbable suture.The wound was closed in layers.

The animals were closely followed postoperativelyto ensure an adequate airway. No stridor developed. Inthe early postoperative period, wound infections de­veloped in two animals that responded promptly to

662 SERCARZ et 01.Ololaryngology­

Head and Neck Surgery

THYROHYOIDMEMBRANE

Fig. 4. Drawing depicts a human larynx and the relnnervotlon scheme used in two of the chroniccanine studies.The cut TAbranch is anastomosed to the sternothyroid branch of the ansa cervicalis.

drainage and antibiotics. Humane animal care was as­sured in compliance with The Principles ofLaboratoryAnimal Care, formulated by the National Society forMedical Research and the Guide for the Care and Use

Fig. 5. Relationship between RLN stimulation and subglotticpressure in an acute experiment before and after denervoftonof the terminal branch of the RLN. There is a lack of increasein subglottic pressure after denervotion, RLN stimulus: low, 0.4rnA; medium, 0.8 rnA; medium-high, 1.6rnA; high, 5.0 rnA,

···-_·····--·········'0···-··············----0·········---- '0

ofLaboratory Animals, prepared by the National Acad­emy of Sciences and published by the National Insti­tutes of Health (NIH publication no. 80-23, revised1978).

After a 4-month survival period, vocal function wasevaluated in all four canines using the in vivo caninestudies outlined previously for the acute animals. Spe­cifically, in each animal RLN and SLN were stimulatedwith monitoring of the subglottic pressure, PGG, andEGG. The effect of a gradual rise in nerve stimulationon subglottic pressure was assessed.

In addition, electromyographic (EMG) recordingswere performed on the four chronic animals 4 monthsafter bilateral TA denervation. A concentric EMG nee­dle electrode placed transorally into the thyroarytenoidmuscle was used. Recordings were performed on eithera TECA TE4 (Pleasantville, N.Y.) or Nicolet VikingII EMG instrument. The signal was high-pass filteredat 20 hertz and low-pass filtered at 10 kHz. The outputwas digitized at 20 kHz and recorded onto the harddrive of a personal computer and the waveforms wereanalyzed with a speech analysis program.

Evoked electromyography was performed in animals

HIGHMEDIHIGHMED

RLN Stimulation

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LOW

100

80

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0

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3 and 4 (reinnervated subjects) by stimulating the ansacervicalis with a Harvard miniature electrode with asingle 0.05 msec pulse of sufficient voltage (10 to 35V) to obtain an adequate contraction. The response wasdetected with a bipolar needle placed transorally intothe ipsilateral TA muscle. The signal was similarly dig­itized at 20 kHz and stored in a personal computer.

Acoustic analysis of the chronic animals' inducedphonation was performed using a commercial softwareprogram (C-Speech, Paul Milenkovic, University ofWisconsin, Madison, Wis.). litter (frequency pertur­bation) and shimmer (amplitude perturbation) were cal­culated on the basis of approximately 0.3 seconds ofstable phonation from each trial. Three measures ofjitter and shimmer were calculated for each subject andaveraged. The background noise in the experimentalquarters was 35 dB lower than the measured values.To normalize for varying fundamental frequency, jitterwas calculated as a fraction of the period of the fun­damental frequency.

Vocal fold mucosa and thyroarytenoid muscle tissuewere excised from the chronic animals, cut in coronalsection, and stained with hematoxylin and eosin to as­sess the histologic effects of denervation I reinnervation.

RESULTS

During high levels of RLN stimulation in the acutesetting, subglottic pressure reached as high as 90 mmHg before denervation, but remained below 30 mm Hgafter denervation. As discussed later, these high pre­denervation pressures are consistent with a previous invivo canine representation of spasmodic dysphonia. 12

It should be noted that all animals retained full vocalfold abduction and adduction and could be electricallyinduced to phonate after TA denervation. Physiologicmotion was verified by occluding the endotracheal tubeat a light plain of anesthesia and observing for vocalfold abduction. The pharynx was stimulated to dem­onstrate vocal fold adduction. This movement was ver­ified on videotape.

Figure 5 shows representative data for one animalrelating subglottic pressure to RLN stimulation beforeand after bilateral acute TA denervation. A similar re­lationship was obtained for each animal, demonstratingthat subglottic pressure increased linearly with increas­ing RLN stimulation predenervation and was indepen­dent of RLN stimulation after the procedure.

Figure 6 shows sample glottographic data in one ofthe acute animals before and after bilateral TA dener­vation. The waveforms are similar, indicating that thechanges in vocal fold tension produced by the proceduredid not impact significantly on EGG and PGG wave­forms, suggesting a similar geometry of laryngeal vi­bration.

Bilateral thyroarytenoid denervation 663

Four chronic animals were studied after bilateral TAdenervation. Figure 7 is the computer printout of sub­glottic pressure during a 2.0-second period of phonationof one animal (animal 1) 4 months after TA denervationwithout reinnervation. There was a persistence of therelationship between subglottic pressure and RLN stim­ulation, corresponding to the postoperative acute stud­ies. Subglottic pressure is observed not to rise despiteincreasing RLN stimulation (to supraphysiologic levels)at constant SLN stimulation. Each of the four chronic(survival) animals had this relationship between sub­glottic pressure and RLN stimulation, with or withoutansa reinnervation.

Figure 8 is a resting EMG recording from the rightdenervated TA muscle in chronic animal 2. A series offibrillation potentials were demonstrated, indicating de­nervation of the monitored muscle. Figure 9 is anevoked EMG from animal 3, 4 months after TA rein­nervation with the ansa cervicalis. The stimulated nervewas the trunk of the ansa, and the monitored musclewas the TA. The small spike represents the stimulusartifact. The second, larger spike is the compound mus­cle action potential (CMAP). The large evoked CMAPdemonstrates reinnervation of the monitored muscle. Avideo photograph (Fig. 10) illustrates the appearanceof the bulge in TA fibers on stimulus during the evokedEMG.

A spontaneous recording EMG from the reinnervatedTA muscle of animal 4 is reproduced in Fig. 11. Ahigh-amplitude long-duration polyphasic motor unit po­tential is shown, a characteristic finding in EMG re­cordings of reinnervated muscle. A series (>20) ofthese potentials was observed in the reinnervated ani­mals, two of which are recorded in the Figure.

Videostroboscopic analysis of the four chronic ani­mals indicated differences between the two deinner­vated animals and the two that underwent reinnervation.Animals 3 and 4 (ansa reinnervation) demonstratedcomplete glottic closure, symmetry of vibration, andtwo mass motion. Animal I (denervation only) hadasymmetric laryngeal tension, with diminished mucosalwave on the right. Animal 2 (denervation only) did notsustain stroboscopic synchronization, as a result of el­evated frequency perturbation.

Figure 12 is a histologic section from a denervatedTA muscle (animal 2). There is marked atrophy of theremaining muscle cells. Figure 13 is a histologic sectionfrom the TA muscle in an animal reinnervated with theansa cervicalis. The reinnervated animals showed someareas with atrophy of TA fibers, whereas others hadnear-normal appearance.

Table I is a summary of data from the chronic studies,including jitter and shimmer data. Although only twoanimals comprised each group, it appears that the non-

664 SERCARZ et 01.Ololaryngology­

Head and Neck Surgery

A /-L/-~\///'--V'Vl

EGG~~~~PGG

dEGG

BEFORE DEINNERVATION

AFTER DEINNERVATION

Fig. 6. Photoglottography (PGG), electroglottography (EGG) and firstderivative of EGG in an acutesublect A, before and B, ofter TAdenervation.

SubglotticPressure(mmHg)

40

20

Low Med Med-High High

RLN STIMULATION

Fig. 7. Raw data of relationship between RLN stimulation and subglottic pressure in chronic animalno. 3 months after denervation of TA branch of RLN, RLN stimulus: low, 0.4 mA; medium, 0,8 mA;medium-high 1.6 rnA; high. 5.0 mAo

Fig. 8. EMG recording from chronic animal 2 shows fibrillationpotentials.

Fig. 9. Evoked EMG from chronic animal 3 with compoundmuscle action potential. Baseline to peak amplitude was 1.2mV.

Time (milliseconds)o 100 200 300Time (milliseconds)

o 20 40

Volume 107 Number 5November 1992 Bilateral thyroarytenoid denervation 665

Fig. 10. Videophotograph documents bUiging of left TAfibers of chronic animal 3 during evokedEMGrecording. The stimuluswas to the left ansa cervicalis stimulation, the source of TAreinnervation.The needle electrode is in place in the TAmuscle.

reinnervated animals had greater frequency and ampli­tude perturbations during induced phonation.

DISCUSSION

No treatment for spasmodic dysphonia has been com­pletely satisfactory, prompting clinicians to continue toseek an effective solution. Fourteen years after Ded04

suggested that RLN section could revolutionize thetreatment of this enigmatic disorder, no single perma­nent therapy has emerged with widespread adherence.

Clinical experience with Botox action on the TA bi­laterally was the primary stimulus for this research. AsLudlow et al." stated in their study of Botox for ASD,"Symptom reduction occurred only when there was areduction in thyroarytenoid muscle activation, sug­gesting that this disorder involves hyperactivity of thismuscle during speech." If the TA muscle could be bi­laterally denervated without loss of normal vocal cordmotion, it was hoped that this treatment would be apermanent analog of botulinum toxin injection.

By performing bilateral TA denervation in the caninemodel, several issues related to the procedure were re­solved. It was found that the terminal branch of theanterior division of the RLN could be easily located.Our cadaver dissections of human larynx and a reviewof the literature suggested a similar course in humanlarynges. II Normal vocal cord abduction and adductionwas verified in all canines after bilateral TA denerva­tion. Finally, bilateral TA denervation altered laryngealfunction in a manner consistent with alleviation of ASDsymptoms.

DELAY: -1 DIU 5 ms

0,4 mvIV-- .:\ . .

~

lIE

Fig.11. Spontaneous EMGfrom chronic animal 4 demonstratesa high-amplitude long-duration polyphasic motor unit po­tential.

Physiologic studies, both in human beings with ASDand in canine research models of hyperadduction dis­orders, have shed light on the relationship between TAtension, subglottic pressure (P,), and the vocal pathol­ogy in ASD.

The canine experience will be discussed first. Hy­peradduction of the true vocal folds is expected to resultin transiently high P,. A canine model of spasmodicdysphonia by Green and Berke" demonstrated signif­icant elevation of P, when the vocal cords were surgi­cally hyperadducted to simulate ASD. It was alsoshown that the hyperadduction of the arytenoids alonewas insufficient to raise subglottic pressure without

666 SERCARZ et 01.Olo(aryngology­

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Flg.12. Photomicrograph showssignificant atrophy of muscle cells in chronic animal 2. (Hematoxylin­eosin stain; original magnification x 128.)

Fig. 13. True vocal cord of chronic animal 3 demonstrates some atrophic and some normal-ap­pearing TAmuscle cells. (Hematoxylin-eosin stain; original magnification x 128.)

forceful contraction of the TA. Green and Berke's" dataalso indicated that the TA muscle, not the cricothyroidmuscle, was primarily responsible for changes in in­traglottic pressure in the presence of vocal process hy­peradduction. This implied that the TA controls P, byits effect on intralaryngeal medial stiffness.

Increasing stimulation of the RLN under conditionsof constant cricothyroid tension produces a gradual risein subglottic pressure in the normal canine. This risecan be observed even under conditions of maximal vo-

cal process contact force. 12.14 This effect of RLN stim­ulation on Ps was abolished with TA denervation in allacute and chronic animals in the present study.

Data in human beings have provided insight intoASD aerodynamics and shown the importance of theTA muscle and high P, in the etiology of ASD. Shippet al. 15 studied P, in human beings with ASD. P, wasderived from intraesophageal pressure in a methodshown to be comparable to measures obtained transtra­cheally. The authors found that in the two patients stud-

Volume 107 Number5November 1992 Bilateral thyroarytenoid denervation 667

Table 1. Characteristics of chronic animals

Subject/No. Stroboscopic EMG data: fAprocedure characteristics muscle Jitter Shimmer Pathology of fA

TA deinnervation Assymetric vibration Fibrillation potentials 0.336 57.9% Marked atrophyTVC laxity (Fig 8) Early TVC fibrosis2 mass motion (Fig. 12)

2 TA deinnervation Poor stroboscopic Fibrillation potentials 0069 7.05% Marked TA atrophysynchronization Early TVC tibrosis

TVC laxity3 TA reinnervation with ansa Symmetrical two Rare fibrillation po- 0.015 5.59% Focal atrophy ot TA

cervicalis mass motion tentials Normai muscle focallyTVC laxity Evoked CMAP

(Fig 9)4 TA reinnervation with ansa Symmetrical two Rare fibrillation po- 0.010 1.38% Focal atrophy of TA

cervical is mass motion tentials Normal muscle focallyTVC laxity Evoked: CMAP

Polyphasic motorunit potential(Fig 11)

CMAP, Compound muscle action potential, TA, thyroarytenoid muscle: EMG, electromyography: TVC, true vocal cord.

ied, both average P, and P, perturbations were increasedmarkedly in ASD patients. Previous studies have in­dependently shown that vocalization produced at highP, (such as the P, measured by Shipp et al. in the ASDpatients) is perceived as "strained" or overpressurized. 16

In another human physiologic study, Ludlow et al. 17

studied intrinsic laryngeal muscles in five patients withASD and five control subjects. The authors found ab­normally high levels of muscular activity in the TA andcricothyroid muscles. 17

Research on human beings and animals to date cor­roborates the notion that the deficiency observed inASD is related to abnormally high intralaryngeal medialadductory pressures mediated by TA muscular contrac­tion. In ASD patients, dysfluency results because thepulmonary expiratory pressure is frequently too low toovercome the abnormally elevated intralaryngeal stiff­ness. This results in phonation that is difficult to sustainduring normal conversational intensity levels.

Because the bilateral selective TA denervation pro­cedure creates an inability to generate elevated intra­glottic and secondarily subglottic pressures, it wouldevidently be helpful in patients with the strained speechcharacteristic of ASD. This is also supported by ex­perience in human beings with Botox.

In comparing the animals with ansa reinnervation tothe TA denervated animals, there were several differ­ences (Table 1). First. there was less TA atrophy in thereinnervated animals (Figs. 12 and 13). Second. thestroboscopic characteristics of induced phonation re­vealed more normal traveling wave motion. Third. thereappeared to be a reduction of jitter and shimmer, al-

though the data included only two subjects in eachgroup.

Bilateral TA denervation with ansa reinnervationshould not be prone to the type of failure associatedwith RLN section. This is because the effects are bi­lateral and do not require vocal fold paralysis to beeffective. Also, because the nerve is reinnervated bythe ansa, unwanted reinnervation by the cut TA nervestump is unlikely. On the basis of the experience withBotox, recurrence by compensation of other muscles isnot expected. Only long-term followup in human beingsguarantees the longevity of any approach to the treat­ment of spasmodic dysphonia. Furthermore, becausethe procedure creates a permanent alteration of laryn­geal function, it would be used only in patients withsevere symptoms.

There are theoretical concerns regarding bilateral TAdenervation. One possible complication is injury to theLCA branch of the RLN. This should be avoidable,because the branch to the LCA is significantly proximalto the location of the window, as illustrated in Fig. 1.The voice characteristics produced by the procedure areunknown. Experience with Botox and the in vivo caninemodel would suggest that the voice produced will beacceptable.

One of the secondary goals of this study was to provethat the thyroid cartilage should not be considered asthe limiting barrier to laryngeal phonosurgical manip­ulation. We have successfully demonstrated that theindividual neuromuscular elements comprising the lar­ynx can be accessed and modified to predictably affectlaryngeal functioning. It is apparent that just beyond

668 SERCARZ et 01.

the horizon exists a wide variety of new procedures,based on current knowledge of laryngeal anatomy andbiomechanics. Hopefully this study has brought uscloser to it.

REFERENCES

I. Schaefer SD. Neuropathology of spasmodic dysphonia. Laryn­goscope 1983;93:1183-204.

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