NEUROLOGICAL REVIEW SECTION EDITOR: DAVID E. PLEASURE, MD Vocal Cord Dysfunction in Amyotrophic Lateral Sclerosis Four Cases and a Review of the Literature Maaike M. van der Graaff, MD; Wilko Grolman, MD, PhD; Erik J. Westermann, MD; Hans C. Boogaardt; Hans Koelman, MD, PhD; Anneke J. van der Kooi, MD, PhD; Marina A. Tijssen, MD, PhD; Marianne de Visser, MD, PhD e describe 4 patients with amyotrophic lateral sclerosis (ALS) and glottic nar- rowing due to vocal cord dysfunction, and review the literature found using the following search terms: amyotrophic lateral sclerosis, motor neuron disease, stri- dor, laryngospasm, vocal cord abductor paresis, and hoarseness. Neurological Wliterature rarely reports vocal cord dysfunction in ALS, in contrast to otolaryngology literature (4%- 30% of patients with ALS). Both infranuclear and supranuclear mechanisms may play a role. Vocal cord dysfunction can occur at any stage of disease and may account for sudden death in ALS. Treat- ment of severe cases includes acute airway management and tracheotomy. Arch Neurol. 2009;66(11):1329-1333 Amyotrophic lateral sclerosis (ALS) is a neu- (VCAP), it is potentially life threatening, as rodegenerative disease characterized by fea- a predominance of vocal cord adduction re- tures indicative of both upper and lower sults in glottic narrowing or even occlu- motor neuron degeneration. Initial manifes- sion. Assessment by an otolaryngologist is tations usually include weakness in the bul- then of the highest priority. Stridor is a well- bar region or weakness of the limbs. Progres- known symptom in multiple system atro- sive weakness leads to increasing disability phy and may also incidentally occur in other and respiratory insufficiency, resulting in neurodegenerative diseases.8-10 Laryngo- death. The median survival time is 2.5 to 3 spasm, a sudden and uncontrollable clo- yearsfromonsetofsymptoms;the5-yearsur- sure of the larynx, is another symptom of vival rate is approximately 25% to 30%.1,2 vocal cord dysfunction.11 Laryngeal elec- Dyspnea is a frequent and well-known tromyography may be helpful in the diag- symptom in patients with ALS and occurs nosis of vocal cord dysfunction.12 when respiratory muscles become weak. Wedescribe4patientswithALSandacute However, acute dyspnea may also be the re- dyspnea due to vocal cord dysfunction re- sult of glottic narrowing due to paresis of sultinginglotticnarrowing.Threedeveloped the vocal cord abductors. Vocal cord dys- the symptoms in the course of their disease; function has received little attention in ALS in the fourth patient, they were present at literature. the time of diagnosis. We also review the lit- Symptoms of vocal cord dysfunction erature on this subject. Search terms in- range from hoarseness, hypophonia, and cluded: amyotrophic lateral sclerosis, mo- short phonation time to nocturnal nonpro- tor neuron disease, stridor, laryngospasm, ductive cough and attacks of inspiratory stri- vocal cord abductor paresis, hoarseness, and dor and dyspnea.3-6 Inspiratory stridor is de- multiplesystematrophy.Relevantreferences fined as a harsh, strained sound with a in publications were hand searched. higher pitch than snoring.7 When stridor is caused by vocal cord abduction paresis REPORT OF CASES Author Affiliations: Departments of Neurology (Drs van der Graaff, van der Kooi, Patient 1 Tijssen, and de Visser), Otolaryngology (Dr Grolman and Mr Boogaardt), and Neurophysiology (Dr Koelman), Academic Medical Center, Amsterdam; and A 56-year-old woman presented with Center for Home Mechanical Ventilation (Dr Westermann), University Medical weakness, atrophy, and hyperreflexia of Center Utrecht, Utrecht, the Netherlands. her right arm and was diagnosed with fa- (REPRINTED) ARCH NEUROL / VOL 66 (NO. 11), NOV 2009 WWW.ARCHNEUROL.COM 1329 ©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 milial superoxide dismutase 1–negative ALS. Three of her thereafter, she had respiratory failure and received me- brothers and 2 paternal cousins had died of ALS. Dis- chanical ventilation. A few months later, she expressed the ease progression comprised atrophic tetraplegia and dys- wish to die. After a careful evaluation of her condition, her arthria, with hyperreflexia in the limbs but only lower mo- request for euthanasia was granted. tor neuron signs in the bulbar region. Four years after diagnosis she experienced 6 attacks (4 of them nocturnal) Patient 4 of acute dyspnea, during which she felt an involuntary air- way closure. Laryngoscopy showed paresis of vocal cord A 69-year-old man was referred to our neurology depart- abduction, and a tracheotomy was performed. Vital capac- ment with progressive dysarthria, dysphagia, and pseudo- ity (VC) was still 100% of that predicted, and findings of bulbar affect present for 1.5 years. He also experienced daily arterial blood gas analysis were normal. She died 1 year later attacks of acute dyspnea with a sensation as if his throat of respiratory failure after an episode of rapidly declining were compressed, usually provoked by aspiration or by a VC because she refused to be mechanically ventilated. None supine position. He had signs of upper and lower motor of her affected family members had had a history of vocal neuron involvement in the bulbar region. Results of neu- cord problems, but they had never been examined by an rological examination of the limbs were normal but needle otolaryngologist. EMG showed spontaneous activity and reinnervation in the trunk and leg region. A diagnosis of sporadic probable labo- Patient 2 ratory-supported ALS was made. His VC was 95% of pre- dicted. Laryngoscopy triggered a laryngospasm with un- A 63-year-old man visited an otolaryngologist because controlled adduction of the vocal cords lasting for 1 minute. of dysarthria and dysphagia for 1 year. Laryngoscopy re- Needle EMG of the (adducting) vocal muscle revealed tonic vealed no abnormalities of the vocal cords. He was then activation in rest (Figure 1A). Motor units appeared nor- referred to a neurologist. Upper motor neuron signs (pseu- mal. Needle EMG of the (abducting) posterior cricoaryte- dobulbar affect) were prominent in the bulbar region but noid muscle showed no signs of denervation but polypha- he also had some atrophy of the tongue. Neurological ex- sic motor unit action potentials of long duration were amination and results of needle electromyography (EMG) compatible with reinnervation and a markedly reduced in- of the limbs appeared normal, as did brain magnetic reso- terference pattern during inspiration (Figure 1B). Results nance imaging. His VC was 95% of predicted. A diagno- of blood gas analysis were normal. A tracheotomy was per- sis of sporadic possible ALS with bulbar onset accord- formed shortly thereafter. A follow-up laryngoscopy after ing to the revised El Escorial13 criteria was made. Some tracheotomy revealed an almost midline position of the vo- months later he had widespread fasciculations in his arms cal cords at inspiration (Figure 2A). He is now anarthric, and legs with still normal strength, brisk reflexes, and uses percutaneous endoscopic gastrostomy feeding, and is an equivocal plantar response. still ambulant but has weakness in his right arm. Nearly 1 year later he had an attack of acute dyspnea and stridor at night. Laryngoscopy revealed vocal cord REVIEW OF THE LITERATURE abduction paresis; subsequently, tracheotomy was per- formed. One year after tracheotomy he experienced res- Epidemiology piratory failure. He chose not to be mechanically venti- lated and died shortly thereafter, 4 years after onset of Vocal cord abductor paresis and laryngospasm in ALS are symptoms. rarely described in the neurological literature. There are 3 superoxide dismutase 1–positive Japanese cases of ALS pre- Patient 3 senting with hoarseness due to bilateral vocal cord pare- sis as an initial manifestation of the disease.3,6 A large sur- A 58-year-old woman visited a neurologist because of vey of clinicians’ practice in the symptomatic treatment of slurred speech and dysphagia. She had signs of upper and ALS in the United States recognized that laryngospasm is lower motor neuron involvement in the bulbar region. seldom mentioned in ALS literature but is present in 19% Neither neurological examination nor needle EMG of patients when queried.14 A study of expiratory muscle showed abnormalities in the limbs. A brain magnetic reso- function in patients with ALS found abnormal function of nance image appeared normal. A diagnosis of sporadic the vocal cords in 2 of 11 patients with respiratory symp- possible ALS with bulbar onset was made. Her VC was toms.15 In this study, patients without respiratory symp- 130% of predicted. At a later stage of the disease, she de- toms did not have laryngoscopy. A study using a symp- veloped weakness of the hands. tom questionnaire but no fiberoptic analysis of the vocal One year after onset of symptoms, she incidentally felt cords reported laryngospasm in 2% of 147 patients with sudden spasms of her throat following aspiration, leading ALS.16 This study stressed the role of pyrosis in some cases. to cyanosis. These spasms were very concerning to her. Per- It is known that laryngospasm may be triggered by aspi- formance of percutaneous endoscopic gastrostomy was ration of refluxed gastric contents, and an intense antire- complicated by laryngospasm. She was referred to an oto- flux treatment can abolish the attacks of dyspnea.14,17,18 laryngologist who confirmed paresis of the vocal cord ab- In contrast, otolaryngology literature addresses VCAP ductors with both vocal cords almost in midline position. and laryngospasm in ALS more often. Hoarseness was She was advised to have tracheotomy, which she initially noted as the initial manifestation in 3.9% of 441 pa- declined, but eventually a tracheotomy was performed. Re- tients with ALS being seen by an otolaryngologist.19 A sults of capillary blood gas analysis were still normal. Shortly large cohort study that included more than 100 patients (REPRINTED) ARCH NEUROL / VOL 66 (NO. 11), NOV 2009 WWW.ARCHNEUROL.COM 1330 ©2009 American Medical Association.