Familial Vocal Cord Dysfunction

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Familial

Vocal Cord Dysfunction

Michael J. Cunningham, MD, Roland D. Eavey, MD, and

Daniel C. Shannon, MD

From the Department of Otolaryngology of the Massachusetts Eye and Ear Infirmary, the Pediatric Pulmonary Research Unit and Children’s Service of the Massachusetts General Hospital, and the Departments of Otolaryngology and Pediatrics of the Harvard Medical School, Boston

ABSTRACT. Vocal cord paralysis is a common cause of neonatal stridor. Familial vocal cord dysfunction, how-ever, is unusual. All three siblings in one family had neonatal stridor. Vocal cord dysfunction was confirmed after endoscopic examination in two of the children; a

temporary tracheotomy was required by one child.

Re-sults of evaluation, including pulmonary function tests, suggest discrete dysfunction localized to the neuromus-cular pathway responsible for vocal cord abduction. En-doscopy is of prime importance in the diagnosis of vocal cord dysfunction. In considering therapy, the physician

must weigh both the potentially life-threatening nature of vocal cord paralysis, as well as the likelihood of even-tual spontaneous resolution of many familial and idio-pathic cases. Pediatrics 1985;76:750-753; neonatal stridor, vocal cord paralysis, vocal cord paresis, heredity, nucleus ambiguus.

Stridor in the newborn indicates airway

obstruc-tion. Numerous etiologies can produce this

symp-tom.’ Vocal cord paralysis and paresis rank as the

second most common cause.24 We document vocal

cord dysfunction in a brother and sister and suspect

the same in a third sibling. All three presented with inspiratory stridor at birth. Despite the frequency

of vocal

cord

paralysis/paresis,

familial

cases are

rare; none have been recorded in the pediatric

lit-erature.59

CASE REPORTS

Case 1

R.B., a 3,120-g male infant, was born to a healthy 22-year-old mother by spontaneous vaginal delivery

follow-Received for publication June 25, 1984; accepted Feb 7, 1985.

Reprint requests to (R.D.E.) Department of Otolaryngology,

Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston,

MA 02114.

ing an uncomplicated full-term pregnancy. From

birth,

he demonstrated noisy breathing exacerbated by crying. At 6 weeks of age he was admitted to another hospital for evaluation of a one-minute cyanotic episode. Results of the following tests were normal: complete blood cell counts, fluorescent antibody screen, culture for pertussis, electrocardiogram, chest and lateral neck radiography,

and pneumogram. An otolaryngology consultant

per-formed a laryngoscopy at the bedside, diagnosed “laryn-gomalacia,” and recommended no further evaluation. Be-cause of continued stridor and respiratory distress, R.B. was transferred to the Children’s Service of the Massa-chusetts General Hospital when he was 7 weeks of age.

Physical examination at that time revealed a 3,900-g (third percentile), 54-cm long (third percentile) male infant whose head circumference measured 38 cm (75th percentile). He was found to have systemic hypertension, with cuff pressures as high as 180/100 mm Hg. Positive physical findings, including thorough neurologic

evalua-tion, were otherwise limited to the respiratory tract. Lying quietly, the baby had mild suprasternal retractions and barely audible inspiratory stridor. With agitation, marked intercostal and subcostal retractions, nasal flare,

and very loud inspiratory stridor became evident. He

remained acyanotic. His cry varied from muffled to nor-mal. Elicited cough was normal. The stridor was heard

with a stethoscope best over the anterior midline neck.

Fremitus was palpable over the same region.

Results of arterial blood gas’ studies with the baby breathing room air revealed hypoxia and hypercarbia

(Po2, 53 mm Hg, Pco2, 51 mm Hg; pH 7.31 HCO3, 25

mEqJL). A computed tomographic scan of the head and

auditory-evoked response study were normal. A barium swallow fluoroscopic study demonstrated intact anatomy and normal gastroesophageal function. A sweat chloride

test was negative. A renovascular hypertension work-up,

including urinalysis, creatinine clearance, urine vanillyl-mandelic acid to creatinine ratio, urine epinephrine and norepinephrine levels, renal ultrasound, and renal scan,

was unrevealing. Administration of spironolactone (Al-dactone) and chlorothiazide (Diuril) failed to control the

systemic hypertension.

Endoscopy was performed under general anesthesia

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supra

-TABLE. Ventilation Parameters Recorded From Patient R.B. When Breathing Air, 3.5%

CO2, 100% 02, and 15% 02*

Vs/kg (L/min)

Pco2

(mm Hg)

VT/Ti (L/s)

Ti/Ttot (s)

TcPo2

(mm Hg)

Air 538-590 36-39 69-77 0.47-0.49 46-52

3.5% CO2 765 50 100 0.48 61

100% 02

Baseline 577 33.7 76 0.49 47

10 5 555 34.2 74 0.49 54

20s 520 34.0 64 0.49 117

300 s 691 29 90 0.48 158

15% 02

Baseline 576 37 74 0.47 53

20 s 589 36.5 . 77 0.48 44

40 s 508 38.2 64 0.47 41

60 s 545 35.7 73 0.48 39

* All values represent the average of 100-second intervals unless otherwise indicated. Abbreviations used are: VE, minute ventilation; Pco2, partial pressure of CO2; VT, tital

volume; Ti, inspiratory time; Ttot, total inspiration-expiration time; TcPo2, transcutane-ous partial pressure of 02.

ARTICLES 751

glottic structures appeared normal. Lifting the epiglottis with the laryngoscope did not cease the audible stridor. The vocal cords were observed in a midiine position (Fig, left), with a 1-mm opening between the cords evident on

expiration. On inspiration the cords paradoxically

ap-proached one another, further narrowing the airway.

Passive cord motion tested with a laryngeal spatula was

normal. Intubation with a 3.0-mm endotracheal tube

eliminated the stridor. Normal subglottic, tracheal, and bronchial structures were seen on bronchoscopic

exami-nation. A tracheotomy was performed.

In the immediate postoperative period, systemic blood pressure normalized, and arterial gas values improved

markedly (P02, 91 mm Hg; Pco2, 38 mm Hg; pH 7.49;

HCO3, 29 mEqJL). The elevated plasma bicarbonate

value, however, indicated chronic hypoventilation due either to a failure of central respiratory drive or severe airflow obstruction. Pulmonary function testing was per-formed to assess brainstem-mediated ventilatory control reflexes (Table). The ventilatory responses to 3.5% CO2

Figure. Left (case 1): Vocal cords at maximum

abduc-tion. With inspiration, cords further adduct paradoxically (arrows). Dotted lines indicate approximate normal

po-sition for inspiration. Right (case 2): Vocal cords at rest. Minimal abduction occurred with inspiration (arrows).

in air, 15% 02, and 100% 02 were measured and compared with our laboratory standards for the appropriate age and

state.’#{176}The ventilatory response to hypercarbia (3.5% CO2) was at the third percentile, the response to

hyper-oxia (100% 02) was appropriate, and there was no

de-monstrable response to moderately severe hypoxia

(transcutaneous P02, 39 mm Hg). This level of hypoxia is comparable to that expected in a healthy infant breath-ing 12% 02. The duty cycle (inspiratory time/total

inspi-ration-expiration time) during which the diaphragm is

contracting, was similar under all conditions. The

in-spired flow rate was similar during episodes of air

breath-ing, increased under the influence of added CO2, and

decreased during hypoxia when an increase in flow rate is expected.

The infant was discharged from the hospital to home on the 13th postoperative day with a well-functioning

tracheostomy. Systolic blood pressure values had

re-mained in the 90- to 100-mm Hg range since the

opera-tion. Arterial blood gas values 1 month following hospital discharge were normal (Po2, 92 mmHg; Pco2, 39 mm Hg-, pH 7.39; HCO3, 23 mEciJL).

Endoscopic examinations during the ensuing 20

months demonstrated slowly improving vocal cord func-tion. The glottic airway enlarged to 2.0 to 3.0 mm, allow-ing successful decannulation at the age of 22 months. At

26 months, his weight and height were at the 25th and tenth percentiles, respectively. There was no delay in his

speech, motor, or cognitive skills.

Case 2

D.B., the younger sister of R.B., was the 3,005-g

prod-uct of a similar uncomplicated pregnancy and normal

spontaneous vaginal delivery. Inspiratory stridor with crying and agitation was likewise noted in the neonatal

period. The infant was admitted to the Children’s Service

of the Massachusetts General Hospital for evaluation at

4 weeks of age. There was no history of respiratory

distress at rest, apnea, cyanosis, or feeding difficulty. She

was a well-nourished appearing 3,460-g infant who

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breathed quietly and confortably at rest but developed moderate inspiratory stridor when agitated. Stethoscopic examination localized the stridor to the anterior midline neck. No fremitus was palpable. Results of

otolaryngo-logic examination were otherwise within normal limits. The general examination, including systemic blood pres-sure, demonstrated no additional abnormalities.

After initial examination with a flexible endoscope while the baby was awake, laryngoscopy was performed

under general anesthesia while she breathed

sponta-neously. The laryngeal structures were normal. The vocal cords were in a paramedian position (Fig, right) and abducted poorly on inspiration. Passive cord motion was normal. Bronchoscopic results were normal. A diagnosis of bilateral abductor vocal cord paresis was made. Tra-cheotomy was not necessary due to the adequacy of the airway. D.B. tolerated viral infections with slightly in-creased stridor but no distress. By 12 months of age she

became symptom free.

Case 3

L.B., the older sister of R.B. and D.B., is 4 years old. She has had inspiratory stridor since birth with crying, agitation, exertion, and during respiratory illnesses. The stridor has gradually improved throughout the years. She

has never been formally examined due to parental

reluc-tance.

There are no other siblings. There is no maternal family history of obstructive airway disease. Paternal family history is unavailable.

DISCUSSION

Vocal cord paralysis and/or paresis was

demon-strable in 46 of 124 neonates endoscoped by Cohen

et a12 for obstructive symptomatology. Cord

paral-ysis was the second most common pathologic

find-ing in this study. The etiology of this condition was

reviewed in two additional large series of infants

and children with documented vocal cord

paraly-sis.3’4 In approximately two thirds of the cases in

each series, there was a history of antecedent birth

or surgical trauma, associated structural or

func-tional CNS disease, or bulbar paralysis of infectious

or neoplastic

etiology.

In approximately

one third

of the cases, however,

no identifiable

cause or

pre-disposing

condition

could be found.

Rare accounts of familial vocal cord paralysis do

exist.59 Vocal cord dysfunction has been

docu-mented in both male and female family members

across two and three successive generations,

sug-gesting an autosomal dominant mode of

inherit-ance.79 The severity of this familial paralysis is

underscored by the frequent need for tracheotomy

in afflicted individuals,5’7’9 and

by the occurrence

of

neonatal asphyxial deaths or subsequent global

brain damage when tracheotomy was delayed or not

performed.5’6’8 The age of onset of familial vocal

cord

paralysis

has been

variable.

In the

families

described by Gacek7 and by Morelli et al,8

individ-uals were asymptomatic until late infancy,

child-hood, or adolescence. In contrast, our patients, and

the cases reported by Plott5 and by Grundfast and

Milmoe,9 demonstrated symptomatic vocal cord

pa-ralysis or paresis at birth.

Plott5 first suggested that the paralysis in such

cases may be due to an inherited defect in the

brainstem nucleus responsible for vocal cord

func-tion. The posterior cricoarytenoid muscle is the sole

vocal cord abductor. This muscle is innervated only

by neurons in the ventral division of the ipsilateral

nucleus ambiguus. Several other laryngeal muscles

adduct and fix the vocal cords. They, in contrast,

are innervated by a larger number of neurons

dis-tributed throughout the more extensive dorsal

di-visions of this nucleus. Plott5 and Gacek” have

suggested that this anatomic arrangement explains

the particular vulnerability of the neural regulation

of vocal cord abduction to neurologic insult.

Our male patient’s work-up uniquely included an

assessment of ventilatory control reflexes which

are, in part, mediated by the carotid body. These

reflexes project to the nucleus ambiguus and permit

the brainstem to initiate and coordinate the motor

response ofthe diaphragm and airway skeletal

mus-des.12 Indeed, Megirian and Sherry13 have observed

that hypoxia prompts vocal cord abduction. Our

patients’s appropriate reduction in ventilation in

response to hyperoxia and marginally increased

ventilatory response to hypercarbia demonstrate

that chemoreceptor ventilatory control reflex

path-ways are present. The depression of inspiratory flow

rate with hypoxia suggests a poorly responsive

sys-tem, consistent with the documented failure of the

vocal cords to abduct appropriately.

The normalization of systemic blood pressure

values following tracheotomy in case 1 suggests that

the preoperative hypertension was a consequence

of abnormal airway mechanics or gas exchange

secondary to the vocal cord paralysis.

The gradual spontaneous improvement in vocal

cord function demonstrated in this child lends

sup-port to a theoretical maturation of the

neuromus-cular pathway involving the carotid body, nucleus

ambiguus, posterior cricoarytenoid muscles, and

neural connections. No alternative anatomic

path-way is known that could gradually assume control

of vocal cord abduction. A contributory role of

increased glottic airway opening with growth may

further compensate for less-than-ideal vocal cord

abduction.

IMPLICATIONS

Spontaneous recovery of vocal cord function, as

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ARTICLES 753

and sister reported by Grundfast and Milmoe.9 The

clinical course in these two familial cases parallels

the similar gradual improvement observed in many

idiopathic individual cases of vocal cord paralysis.

These observations indicate a favorable prognosis

and support the idea that treatment of the

stridor-ous newborn should be initially conservative,

lim-ited

to those

procedures

necessary

to make

the

proper diagnosis and to ensure an adequate airway.

Diagnosis requires direct visualization of the

im-mobile vocal cord structures. In the newborn,

ex-amination at the bedside with a flexible fiberoptic

laryngoscope or with a rigid endoscope in the

op-erating room, permits such visualization. The latter

preferentially allows manual manipulation of the

cords to distinguish

true paralysis

from

cricoaryte-noid joint fixation and permits observation below

the cords to rule out additional unexpected lesions.

Airway management in the child with

endoscop-ically visualized vocal cord paresis is often

obser-vation alone. More severe bilateral abductor cord

paralysis will require tracheotomy. The family must

be prepared for this possibility whenever the child’s

appearance warrants endoscopic examination.2

More definitve procedures to open the airway such

as arytenoidectomy, cord lateralization, or

cordec-tomy are not warranted initially. When

sponta-neous resolution of the cord paralysis does not

occur, these procedures will permit tracheotomy

tube decannulation and thereby enhance the child’s

quality of life.

SUMMARY

Vocal cord paralysis and paresis are a frequent

cause of neonatal inspiratory stridor and

respira-tory distress. Familial vocal cord dysfunction is a

comparatively rare entity. The work-up of the male

sibling in this case report demonstrates defective

chemical regulation of breathing that theoretically

depends on neural transmission from the carotid

body through the nucleus ambiguus to the posterior

cricoarytenoid muscles. A broader application of

this theory from familial to more common

idio-pathic cases of vocal cord paralysis can be

hypoth-esized given the tendency toward spontaneous

res-olution, perhaps due to pathway maturation, which

is observed in both cases.

REFERENCES

1. Cotton RT, Reilly JS: Stridor and airway obstruction, in

Bluestone C, Stool S (eds): Pediatric Otolaryngology.

Phila-delphia, WB Saunders Co, 1983, pp 1191-1193

2. Cohen SR, Eavey RD, Desmond MS, et al: Endoscopy and

tracheotomy in the neonatal period. Ann Otol Rhinol Lar-yngol 1977;86:577-583

3. Cohen SR, Geller KA, Birns JW, et al: Laryngeal paralysis

in children: A long-term retrospective study. Ann Otol

Rhinol Laryngol 1982;91:417-423

4. Holinger LD, Holinger PC, Holinger PH: Etiology of

bilat-eral vocal cord paralysis: A review of 389 cases. Ann Otol Rhinol Laryngol 1976;85:428-436

5. Plott D: Congenital laryngeal abductor paralysis due to

nucleus ambiguus dysgenesis in three brothers. N EngI J

Med 1964;271:593-596

6. Watters GV, Fitch N: Familial laryngeal abductor paralysis

and psychomotor retardation. Clin Genet 1973;4:429-433

7. Gacek RR: Hereditary abductor vocal cord paralysis. Ann Otol Rhinol Laryngol 1976;85:90-93

8. Morelli G, Mesolella C, Costa F, et al: Familial laryngeal

abductor paralysis with presumed autosomal dominant

in-heritance. Ann Otol Rhinol Laryngol 1982;91:323-324

9. Grundfast KM, Milmoe G: Congenital hereditary bilateral

abductor vocal cord paralysis. Ann Otol Rhinol Laryngol

1982;91:564-566

10. Fagenholz SA, O’Connell K, Shannon DC: Chemoreceptor

function and sleep state in apnea. Pediatrics 1976;58:31-36

1 1. Gacek RR: Localization of laryngeal motor neurons in the

kitten. Laryngoscope 1975;85:1841-1861

12. Pitts RF: Organization of the neural mechanisms

responsi-ble for rythmic respiration, in Fulton JF (ed): Textbook of

Physiology. Philadelphia, WB Saunders Co, 1949, p 822

13. Megirian D, Sherrey J: Respiratory functions of the

laryn-geal muscles during sleep. Sleep 1980;3:289-298

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1985;76;750

Pediatrics

Michael J. Cunningham, Roland D. Eavey and Daniel C. Shannon