The Laryngoscope Lippincott Williams & Wilkins © 2008 The American Laryngological, Rhinological and Otological Society, Inc.
Paradoxical Vocal Fold Motion: A Sensory-Motor Laryngeal Disorder Sabrina Cukier-Blaj, SLP, MS; Arnaud Bewley, MD; Jonathan E. Aviv, MD; Thomas Murry, PhD
Objectives: The purpose of this study is to determine the laryngeal sensitivity (LS) thresholds and the ratings of laryngopharyngeal reflux symptoms in patients with paradoxical vocal fold motion (PVFM). Methods: This is a chart review following Institutional Review Board approval of 75 patients from January 2006 to June 2007. The patients were diagnosed with PVFM following case history, transnasal flexible laryngoscopy and spirometric testing. The data analyzed consisted of the reflux symptom index (RSI) and laryngopharyngeal sensitivity (LS). Laryngeal sensitivity and RSI were graded according to mild, moderate, or severe. Results: There were 12 (16%) patients with normal RSI scores, 37 patients (49.3%) with moderate RSI (RSI 11–22), and 26 patients (34.7%) with severe RSI (RSI ⬎22). The right LS was normal in 11 patients (14.7%), moderately impaired in 16 patients (21.3%), and severely impaired in 48 (64%) patients. The left LS showed normal sensation in 11 patients (14.7%), moderately impaired LS in 13 patients (17.3%), and severe impairment in 51 patients (68%). Only one patient had both normal sensation and normal RSI, and 70.4% of patients had abnormal RSI and sensation thresholds. Conclusions: Patients diagnosed with PVFM had a high prevalence of symptoms related to LPR and markedly reduced LS. These findings suggest that PVFM may be triggered by reduced peripheral sensation or laryngeal inflammation. Key Words: Paradoxical vocal fold motion, laryngopharyngeal reflux, laryngeal sensory deficits. Laryngoscope, 118:367–370, 2008
From the Department of Otolaryngology–Head & Neck Surgery (S.C.-B., Columbia University Medical Center, New York, NY, USA; and the Integrated Acoustic Analysis and Cognition Laboratory (S.C.-B.), Catholic University of Sa˜o Paulo; CEFAC–Health & Education, Sa˜o Paulo, Brazil. Note: Arnaud Bewley is now at the University of Pennsylvania, Department of Otolaryngology–Head and Neck Surgery, Philadelphia, Pennsylvania, U.S.A. Editor’s Note: This Manuscript was accepted for publication August 27, 2007. This research was presented at the American Bronchoesophageal Association at the Combined Otolaryngology Spring Meetings in San Diego, California, U.S.A., April, 26, 2007. Send correspondence to Thomas Murry, PhD, Department of Otolaryngology–Head and Neck Surgery, Columbia University, 180 Fort Washington Ave. HP 8-812, New York, NY 10032, U.S.A. E-mail:
[email protected] A.B., J.E.A., T.M.),
DOI: 10.1097/MLG.0b013e31815988b0
Laryngoscope 118: February 2008
INTRODUCTION Paradoxical vocal fold motion (PVFM) is a condition characterized by the intermittent adduction of more than 50% of the vocal folds during the respiratory cycle, usually during inspiration.1 The most common symptoms are dyspnea, cough, and dysphonia.1,2 PVFM was first described by Patterson in 1974.3 The original designation as “Munchausen’s Stridor” suggested a factitious or conversion disorder.3 Case series supported this hypothesis by describing patients with PVFM who had negative medical workups and a predilection for psychiatric disease.1,3 However, further studies have diminished a psychiatric etiology, bringing out inflammatory and a neurological basis as the main contributors.4,5 Maschka et al.4 proposed that PVFM might represent a spectrum of underlying diseases that manifest as a single clinical entity. His group described cases of PVFM due to medical conditions such as brainstem compression, airway irritant exposure, and laryngopharyngeal and gastroesophageal reflux disease (LPR and GER). The hypothesis that PVFM may result from inflammation was supported by the consistently observed high prevalence of reflux disease in patients.4,6,7 The diagnosis of LPR can be strongly suggested by reflux symptoms8 such as hoarseness, cough and throat clearing, and physical laryngeal examination findings.8 The findings of LPR seen on transnasal flexible laryngoscopy examination consist of: pseudosulcus vocalis, ventricle obliteration, vocal fold edema, diffuse laryngeal edema, and posterior comissure hypertrophy.8 The combination of patient history, physical examination, and laryngeal sensory testing has been demonstrated to be as effective as the double-probe 24-hour pH monitoring (sensitive and specific method of making a diagnosis of LPR) to diagnose laryngopharyngeal reflux disease.9 Other laryngeal abnormalities seen in patients with PVFM are injury to superior laryngeal nerve and/or the inferior laryngeal nerve.10 Lee and Woo10 found that 71% of the patients with sudden-onset cough and laryngospasm had concomitant superior laryngeal nerve or recurrent laryngeal nerve motor neuropathy documented by laryngeal electromyography or videostroboscopy. The treatment for PVFM depends on the case history and diagnostic findings. The underlying pathophysiology may never be fully appreciated. If GER or LPR is diagnosed, the treatment usually begins with proton pump therapy and Cukier-Blaj et al.: Paradoxical Vocal Fold Motion
367
a prokinetic agent.11 Treatments that focus on medication often fail to reduce or eliminate the PFVM symptoms, although they may reduce their severity. Surgical correction occurs rarely in this group, but it has been reported.11 Treatment of PVFM may be a combination of pharmacological and behavioral approaches. For patients with neuropathic etiology, a successful treatment with gabapentin (anticonvulsive) has been documented.10 The behavioral approach consists of a variety of respiratory-based exercises.1,12 Short-term improvements have been seen in various treatments. While many etiologies and treatments have been suggested, the underlying pathophysiology remains only partially described. Reflux has been closely associated with PVFM in the past. To date, only casual evidence has suggested that sensory deficits exist in patients with PVFM. Moreover, the combined contributions of sensory deficits and reflux have not been thoroughly identified in patients with PVFM. Our study focused on the severity of reflux and sensory deficits seen in patients with PVFM. The purpose of our study was to determine the degree of laryngeal sensitivity (LS) thresholds and the ratings of laryngopharyngeal reflux symptoms using the reflux symptom index (RSI) in patients with PVFM. Analysis of the severity of LS and RSI was done to determine if there was a difference in the subjective rating of reflux and the objective measure of LS.
MATERIALS AND METHODS A group of 75 patients were diagnosed with PVFM. Cough was the primary complaint and symptom, and shortness of breath was the secondary symptom in this group. Following approval of the proposed study by the Columbia University Institutional Review Board, the patients were selected from a retrospective medical chart review of the patients seen at the Voice and Swallowing Center at Columbia University Medical Center from January 2006 to June 2007. LPR was determined according to the reflux finding score (RFS) completed by the patient prior to examination and from the physical findings of posterior glottic edema and erythema found in the transnasal flexible laryngoscopy (TFL) examination.8 The diagnostic criteria for PVFM consisted of TFL and flow loop spirometry. The TFL protocol for PFVM has been described in detail previously.7 In summary, patients are observed breathing through their nose and then through their mouth for several seconds once the patient is comfortable. Patients are also asked to say the sentence: “We see three green trees.” Patients with a greater than
50% glottic closure on inhalation during quiet breathing, and following the sentence were diagnosed with PVFM. All patients diagnosed with PVFM underwent flow loop spirometry (KoKo Pneumotach Spirometer, Susquehanna Micro, Inc., Red Lion, PA). The forced vital capacity (FVC), ratio of forced inspiratory volume at 1 second to forced inspiratory vital capacity (FIV1.0/FIVC) and ratio of forced inspiratory volume at 0.5 second to forced inspiratory vital capacity (FIV0.5/FIVC) measures were obtained. Forced vital capacity and forced expiratory volume between 0.25% and 0.75% (FEV25%–75%) were used to determine normal lung function. PVFM is typically characterized by a flattened inspiratory flow-volume loop.7 Reduced FVC was considered as a pulmonary disease and patients with FVC below 80% of their predicted value were excluded in this chart review. The reflux symptom index (RSI) and laryngeal sensitivity (LS) results of these patients were obtained from chart review. RSI represents a previously validated nine-item self-administered measure of laryngopharyngeal reflux (LPR) symptoms.13 According to Belafsky et al.,13 a score higher than 10 strongly suggests LPR. For our study, the categories were determined as follows: a score of less than 11 was considered normal; a score between 11 and 22 was indicative of moderate LPR symptoms; and from 23 to 45 was indicative of severe LPR symptoms. The LS was obtained from sensory testing.14 It consists of a calibrated puff of air delivered to the aryepiglottic fold region of the larynx that identifies the laryngeal adductor reflex (LAR). The LAR pressure threshold has previously been categorized according to normal, moderate, and severely reduced sensation. Normal sensation is considered a pressure threshold of less than 4.0 mm Hg, moderately reduced sensation 4.0 to 6.0 mm Hg, and severely sensory reduction greater than 6.0 mm Hg air pulse.14 The pressure thresholds were obtained in both aryepiglottic fold regions of the larynx.
Statistical Analysis The 2 test was used to determine differences in LS thresholds according to the severity of the RSI. The Student t test was used to compare differences between age and gender for the RSI and for laryngeal sensitivity. A P value of less than 0.05 was considered statistically significant.
RESULTS Clinical Characteristics of the Study Seventy-five patients, 34 male and 41 female, with PVFM were included in this analysis. The mean age was 62 years ⫾ 13.7 years. There was no statistical difference between male and females. Therefore the two groups were combined for the remaining statistical analysis.
TABLE I. Reflux Symptom Classification Scores and Ages of Subjects According to the Reflux Symptom Index. RSI Score RSI Classification
Normal Moderate Severe Total
Age
Number
Percentage
Mean
Standard Deviation
Mean
Standard Deviation
12 37 26 75
16% 49.3% 34.7% 100%
7.5 16 28 19.1
2.2 3 5.8 8.7
67.3 62.7 59.5 62
9 14.4 15.3 13.7
RSI ⬍11 is classified as normal; RSI 11–22 is moderate; RSI 23– 45 is severe. RSI ⫽ Reflux Symptom Index.
Laryngoscope 118: February 2008
368
Cukier-Blaj et al.: Paradoxical Vocal Fold Motion
Characteristics of Reflux Symptoms Index (RSI) The mean RSI for patients with PVFM was 19.1 ⫾ 8.7 (range 4 – 43). There were 12 patients (16%) with normal RSI (RSI ⬍11), 37 (49.3%) with moderate RSI (RSI 11–22), and 26 (34.7%) with severe RSI (RSI ⬎22). The scores of the RSI are shown in Table I.
Characteristics of Laryngeal sensitivity (LS) In patients with PVFM, the mean LS was 6.9 ⫾ 2.1 (range 2.9 –9) in the right side and 7.0 ⫾ 2 (range 2.9 –9) in the left side. The right-side data showed 11 patients (14.7%) with normal LS (LS ⬍4 mm Hg), 16 (21.3%) with moderately impaired LS (LAR at 4 – 6 mm Hg), and 48 (64%) with severely impaired LS (LAR at ⬎6 mm Hg). In the left side, 11 patients (14,7%) had normal LS (LAR at ⬍4 mm Hg), 13 (17.3%) had moderately impaired LS (LAR at 4 – 6 mm Hg), and 51 (68%) had severely impaired LS (LAR at ⬎6 mm Hg). The LAR did not show a statistically significant difference between the sides. The characteristics of the LS are shown in Table II.
TABLE III. Number of Patients With Paradoxical Vocal Fold Motion With Normal and Abnormal Reflux Symptom Index Scores and Laryngopharyngeal Sensitivity Thresholds. Number of Patients Number
Percentage
1 11 10 53
1.3 14.7 13.3 70.7
Normal RSI ⫹ normal LS Normal RSI ⫹ abnormal LS Normal LS ⫹ abnormal RSI Abnormal RSI ⫹ abnormal LS
RSI ⫽ reflux symptom index; LS ⫽ laryngopharyngeal sensitivity.
Statistics When any two RSI groups were compared, there was a significant difference in LS between the normal and the severe RSI groups and between the moderate and severe RSI groups. There was no difference in LS between the normal and moderate RSI groups.
DISCUSSION LS Thresholds and RSI Score The majority of the patients (70.7%) presented abnormal RSI scores (moderate or severe) and abnormal LS thresholds (moderately and severely impaired), while 14.7% of the patients presented normal RSI and abnormal LS thresholds, and 13.3% presented abnormal RSI and normal LS thresholds. Only one patient had normal objective and subjective measures of LS and RSI. The LAR did not show a statistically significant difference between the sides. Therefore data for both sides was combined. These results are shown in Table III. The laryngeal sensitivity can be measured in response to air pulse stimuli and is divided in degrees of normal, moderately impaired, and severely impaired thresholds.14 The LS was found to be markedly reduced in patients with PVFM and asymmetrical in only two patients. The right LS was slightly better, with 14.7% with normal sensitivity; 21.3% with moderately impaired sensitivity; and 64% with severely impaired sensitivity. The left side had 14.7% with normal sensitivity; 17.3% with moderately impaired sensitivity; and 68% with severely impaired sensitivity.
The data analyzed in this study indicated the occurrence of PVFM in adults of both genders. Symptoms of LPR and impaired LS thresholds were both present in patients with PVFM. In our study, only one patient (1.3%) had normal RSI score and normal sensation. Moreover, in 53 (70.7%) patients there was both abnormal sensation and moderate and severe LPR symptoms as indicated by the RSI score. The patients with PVFM had a high prevalence of LPR symptoms (RSI) (49.3% moderate and 34.7% severe) and severely impaired laryngeal sensitivity on both sides of the aryepiglottic fold region. These findings suggest that patients with PVFM have above normal reflux symptoms and decreased laryngeal sensitivity. This is in accordance with previous studies that have also demonstrated a high prevalence of reflux disease and reflux symptoms in patients with PVFM.4,6,7 The finding of abnormal LS in all but one subject supports a sensory deficit hypothesis for patients with PVFM. The current results imply the importance of sensory integrity of the laryngopharynx in maintaining upper airway protection and the prevention of aspiration.15,16
TABLE II. Laryngeal Sensitivity Showing Normal, Moderately Impaired, and Severely Impaired Thresholds According to Age of the Subjects. Threshold Side
Right
Left
Age
Sensitivity
Number
Percentage
Mean
SD
Mean
SD
Normal Moderately impaired Severely impaired Normal Moderately impaired Severely impaired
11 16 48 11 13 51
14.7 21.3 64 14.7 17.3 68
3.6 5 8.2 3.6 5.1 8.2
0.3 0.6 1.1 0.3 0.5 1
61.7 59.7 62.9 61.7 58.4 63
15.3 17.2 12.2 15.3 17.8 12.3
Laryngeal sensitivity thresholds are considered normal if ⬍4.0 mm Hg; moderately impaired 4.0 – 6.0 mm Hg; and severely impaired ⬎6.0 mm Hg.
Laryngoscope 118: February 2008
Cukier-Blaj et al.: Paradoxical Vocal Fold Motion
369
Studies investigating pain in the esophagus support the finding of a sensory deficit in PVFM.17,18 Drewes et al.18 investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization with acid perfusion. Their results showed that sensitization resulted in pain. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions. However there was no difference in the shape of the curve between the before and after acid stimulation, indicating that acid infusion does not change esophageal muscle tone. According to the authors, this illustrated that acid perfusion not only sensitizes the sensory pathways, but also facilitates motor reflexes (for example, cough). The findings of Drewes et al.18 may corroborate the current findings in the larynx. According to Drewes et al.,18 mucosa afferents are often sensitive to different chemical stimuli. The sensitization of afferents encoding seems to change the contractile activity in the muscle via local and/or central reflexes.18 In an analogous situation, the chemoreceptors of the mucosa of the larynx are thought to initiate the reflex that is mediated through vagal connections in the brainstem. Hence, in patients with PVFM, the vocal fold adduction may be accentuated due to the mechanical stimulation or chemical irritation of the laryngeal mucosa (due to LPR), such that various extrinsic stimuli trigger reflexive closure of the vocal folds at pathologically low thresholds.15,19,20 PVFM may therefore represent a compensatory motor response of the efferent fibers in the recurrent laryngeal nerve controlling vocal fold adduction, in response to a hyposensitivity of the afferent fibers of the superior laryngeal nerve. This study suggests that an inflammatory and a neurogenic basis underlie the pathophysiology of PVFM. The lack of sensitivity observed brings us to an interesting point. It suggests that the motor system actively participates in the protective response to the stimuli (including air) in the airway. Given that this was a chart review study of patients diagnosed with PVFM, no control group was examined. However, the results support the need for a multifactorial diagnostic assessment of patients with complaints of hoarseness, cough, or throat clearing. Future studies will allow us to determine the relative values of each of these components to the diagnostic workup of these patients. Further studies involving both electromyographic objective evidence as well as treatment of one or both of the components found in PVFM patients (inflammation, neuropathy) may shed further light on the underlying pathophysiology of PVFM. We submit that PVFM may represent disordered motor and sensory control of laryngeal function. Treatment of patients complaining of cough, hoarseness, and throat clearing is often more empiric than driven by objective testing. The current results offer an appropriate diagnostic protocol to investigate treatments in future prospective studies. Currently, the treatment results from previous studies by one the authors7,12 as well as data from Christopher1 provide an appropriate treatment framework for PVFM.
Laryngoscope 118: February 2008
370
CONCLUSIONS PVFM is a laryngeal sensory and motor disorder with cough and shortness of breath as primary and secondary symptoms. In this study, from a chart review of 75 patients diagnosed with PVFM, 74 were found to have elevated symptoms of laryngopharyngeal reflux and/or laryngeal hyposensitivity.
BIBLIOGRAPHY 1. Christopher KL, Wood RP, Eckert RC, Blager FB, Raney RA, Souhrada JF. Vocal-cord dysfunction presenting as asthma. N Engl J Med 1983;308:1566 –1570. 2. Vertigan AE, Theodoros DG, Gibson PG, Winkworth AL. Voice and upper airway symptoms in people with chronic cough and paradoxical vocal fold movement. J Voice 2007; 21:361–383. 3. Patterson R, Schatz M, Horton M. Munchausen’s stridor: nonorganic laryngeal obstruction. Clin Allergy 1974;4:307–310. 4. Maschka DA, Bauman NM, McCray PB, Hoffman HT, Karnell MP, Smith RJ. A classification scheme for paradoxical vocal cord motion. Laryngoscope 1997;107:1429 –1435. 5. Morrison M, Rammage L, Emami AJ. The irritable larynx syndrome. J Voice 1999;13:447– 455. 6. Altman KW, Mirza N, Ruiz C, Sataloff RT. Paradoxical vocal fold motion: presentation and treatment options. J Voice 2000;14:99 –103. 7. Murry T, Tabaee A, Oxczarzak V, Aviv JE. Respiratory retraining therapy and management of laryngopharyngeal reflux in the treatment of patients with cough and paradoxical vocal fold movement disorder. Ann Otol Rhinol Laryngol 2006;115:754 –758. 8. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS). Laryngoscope 2001;111:1313–1317. 9. Botoman VA. Noncardiac chest pain. J Clin Gastroenterol 2002;34:6 –14. 10. Lee B, Woo P. Chronic cough as a sign of laryngeal sensory neuropathy: diagnosis and treatment. Ann Otol Rhinol Laryngol 2005;114:253–257. 11. Loughlin CJ, Koufman JA. Paroxysmal Laryngospasm secondary to gastroesophageal reflux. Laryngoscope 1996;106: 1502–1505. 12. Murry T, Tabaee A, Aviv JE. Respiratory retraining of refractory cough and laryngopharyngeal reflux in patients with paradoxical vocal fold movement disorder. Laryngoscope 2004;114:1341–1345. 13. Belafsky PC, Postma GN, Amin MR, Koufman JA. Symptoms and findings of laryngopharyngeal reflux. Ear Nose Throat J 2002;81(Suppl 2):10 –13. 14. Aviv JE, Martin JH, Keen MS, Debell M, Blitzer A. Air pulse quantification of supraglottic and pharyngeal sensation: a new technique. Ann Otol Rhinol Laryngol 1993;102:777–780. 15. Aviv JE, Liu H, Parides M, Kaplan ST, Close LG. Laryngopharyngeal sensory deficits in patients with laryngopharyngeal reflux and dysphagia. Ann Otol Rhinol Laryngol 2000;109:1000 –1006. 16. Phua SY, McGarvey LP, Ngu MC, Ing AJ. Patients with gastro-oesophageal reflux disease and cough have impaired laryngopharyngeal mechanosensitivity. Thorax 2005;60:488 – 491. 17. Fass R, Naliboff B, Higa L, et al. Differential effect of longterm esophageal acid exposure on mechanosensitivity and chemosensitivity in humans. Gastroenterology 1998;115: 1363–1373. 18. Drewes AM, Reddy H, Staahl C, et al. Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid. World J Gastroenterol 2005;11: 4367– 4374. 19. Nishino T. Physiological and pathophysiological implications of upper airway reflexes in humans. Japanese Journal of Physiology 2000;50:3–14. 20. Ludlow CL. Central nervous system control of the laryngeal muscles in humans. Respir Physiol Neurobiol 2005;28:147:205–222.
Cukier-Blaj et al.: Paradoxical Vocal Fold Motion
