The Laryngoscope Lippincott Williams & Wilkins, Inc. © 2005 The American Laryngological, Rhinological and Otological Society, Inc.
Cricopharyngeal Muscle Electromyography in Laryngopharyngeal Reflux Mu¨nevver Celik, MD; Zeynep Alkan, MD; Ibrahim Ercan, MD; Hu¨lya Ertasoglu, MD; Canan Alkım, MD; Levent Erdem, MD; Suat Turgut, MD; Cumhur Ertekin, MD
Objectives/Hypothesis: The objective was to determine whether laryngopharyngeal reflux was associated with an electrophysiological abnormality of the main part of the upper esophageal sphincter, namely, the cricopharyngeal muscle, which could be related to laryngopharyngeal reflux symptoms. Study Design: A prospective study of 20 patients with symptoms of laryngopharyngeal reflux. Methods: The diagnosis was based on clinical, laryngoscopic, and ambulatory 24-hour pH monitoring findings. Double-probe pH monitoring was performed with placement of the distal and proximal probes 5 cm above the proximal border of the lower esophageal sphincter and 15 cm proximal to the distal probe, in or just beneath the upper esophageal sphincter. Electromyographic recordings were obtained simultaneously on submental and cricopharyngeal muscles during water swallowing. The peak of the submental electromyographic amplitude and its duration was measured using bipolar surface electrodes placed under the chin. The electromyographic features of the cricopharyngeal muscle were investigated by means of concentric needle electrodes inserted percutaneously both in 20 normal subjects and in 20 patients with laryngopharyngeal reflux. Results: All electrophysiological parameters were normal in all of the patients. The durations of foreburst revealed significant correlation with the number of reflux episodes and acid exposure time (P ⴝ .026 and P ⴝ .044, respectively). Conclusion: The duration of the foreburst correlating with acid exposure time and number of reflux episodes suggested that foreburst duration was extended because of the irritation caused by the acid reflux. Key Words: Deglutition, laryngopharyngeal reflux, dysphagia, cricopharyngeal muscle, upper esophageal sphincter, cricopharyngeal electromyography. Laryngoscope, 115:138 –142, 2005 From the Departments of Neurology (M.C., H.E.), Otolaryngology—Head and Neck Surgery (Z.A., I.E., S.T.), and Gastroenterology (C.A., L.E.), Sisli Etfal Education and Research Hospital, Istanbul Turkey, and the Department of Neurology (C.E.), Ege University Medical Faculty, I˙zmir, Turkey. Editor’s Note: This Manuscript was accepted for publication June 18, 2004. Send Correspondence to Mu¨nevver C ¸ elik, Hu¨srev Gerede caddesi. 128/4 Tesvikiye, 80200 Istanbul, Turkey. E-mail:
[email protected];
[email protected] DOI: 10.1097/01.mlg.0000150690.85387.76
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INTRODUCTION Recently, gastroesophageal reflux (GER), the abnormal reflux of gastric contents into the distal esophagus, has been recognized to be relevant in the explanation of various otolaryngological symptoms.1 Laryngopharyngeal reflux (LPR) has been suggested as a term for the association of laryngeal disorders and GER.2 The most common clinical presentations of LPR include hoarseness, chronic cough, throat clearing, and globus sensation. Dysphagia has also been reported.3 Two mechanisms are implicated in the production of LPR symptoms. The first suggests that acid in the lower esophagus vagally mediates chronic throat clearing and coughing.3 The other proposed mechanism is intermittent reflux of acid into the laryngopharyngeal structures.3,4 Low upper esophageal sphincter (UES) pressures have been implicated in the development of LPR.3 Cricopharyngeal (CP) sphincter muscle is the main part of UES, controlling anterograde and retrograde flow of contents between the pharynx and esophagus during deglutition.5,6 In GER and LPR, videofluoroscopic or endoscopic evaluation of deglutition has been performed in a few studies.7,8 However, electrophysiological testing, which constitutes an easy method of investigating CP muscle and deglutition, has not yet been performed. The aim of the present study was to determine whether LPR is associated with any kind of electrophysiological abnormality of CP muscle, which could be related to the otolaryngological symptoms in patients with LPR.
MATERIALS AND METHODS Patients Electrophysiological examinations of the CP muscle were performed in 20 patients in all (16 women and 4 men) with a recent diagnosis of LPR. The diagnosis was based on clinical, laryngoscopic, and ambulatory 24-hour pH monitoring findings, which are summarized in Table I. The patients ranged in age from 29 to 65 years (mean age ⫾ SD, 46.4 ⫾ 10.7 y). Hoarseness, chronic cough, throat pain, globus sensation, frequent necessity to clear the throat, paroxysmal laryngospasm, and dysphagia were sought. Objective signs of dysphagia (aspiration, cough during swallowing, accumulation of the saliva in the mouth, nasal voice, palatal paresis, abnormal head posture during swallowing) were not detected in any of the patients, although five of them
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TABLE I. Clinical and Ambulatory 24-Hour pH Monitoring Findings. Findings
Clinical findings Hoarseness Chronic cough Throat pain Globus sensation Frequent necessity to clear throat Paroxysmal laryngospasm Dysphagia Laryngoscopical findings Interarytenoid pachydermia Posterior laryngitis Reinke’s edema Vocal nodules Ambulatory 24-hour pH monitoring Acid exposure time No. of reflux episodes
No. of Patients
Mean ⫾ SD (Range)
LPR, that is, hoarseness, severe chronic cough, throat pain, globus sensation, and frequent necessity to clear the throat, and because no general agreement on normal values for the proximal probe yet exists.2,4,9,10
Electrophysiological Methods 20 12 7 19 13 0 5 14 11 6 2 0.84 ⫾ 1.1 (0–4.1) 26.3 ⫾ 24.5 (2–89)
complained of dysphagia. An examiner blinded to the clinical diagnosis performed direct rigid angulated and flexible laryngoscopy to exclude patients who had their symptoms as a result of a laryngeal disease other than LPR (e.g., tumor, vocal cord paralysis) and documented the laryngoscopic findings of patients with LPR. All patients underwent upper gastrointestinal tract endoscopy to exclude concomitant disease and to determine the distance from upper incisor teeth to gastroesophageal junction. The diagnosis of LPR was verified by ambulatory 24-hour pharyngoesophageal pH monitoring, which is considered the gold standard for it.1
The electrophysiological methods used in the present study were previously described.11 Electrophysiological examinations were performed with a Medelec Sapphire 4ME EMG-EP machine while the patient was in the sitting position and the head tilted posteriorly. Bipolar silver-chloride electroencephalographic (EEG) electrodes were taped under the chin over the mylohyoid– geniohyoid–anterior digastric muscle complex to record electromyographic activity referred to as submental electromyogram (SM-EMG). Cricopharyngeal muscle activity was recorded using concentric needle electrodes by passing through the skin in a posterior and medial direction at the level of and just lateral to the cricoid cartilage. The high-frequency tonic EMG activity of the CP muscle when CP muscle was inserted in 2- to 4-cm depth from the skin, the disappearance of this tonic activity during swallowing (CP pause), and the increase in tonic activity before and after the CP pause served as indications of the correct electrode entry into the CP muscle. The SM-EMG and cricopharyngeal electromyogram (CP-EMG) could be recorded band-pass filtered between 100 Hz and 10 kHz and rectified during swallowing. Peak of SM-EMG was used to trigger the delay line circuitry of the recording electrodes on SM and CP muscles so that CP-EMG activity was time-locked to the SM-EMG signal. Total sweep time was set at 2 seconds. At least five recordings during 3-mL water swallowing were obtained. The electrophysiological measurements associated with SM-EMG and CP-EMG (Fig. 1) were as follows: 1) the peak SM-EMG amplitude and its duration, 2) the duration of CP pause, 3) the duration of foreburst and the rising time of rebound burst, and 4) peak amplitudes of the foreburst and rebound burst. To search for electrophysiological abnormalities of the CP muscle in symptomatic patients with LPR, their recordings were
Ambulatory 24-Hour Pharyngoesophageal pH Monitoring Double-probe pH monitoring was performed with twochannel monocrystalline antimony electrodes within a single silicone rubber catheter (diameter, 2.1 mm), with the sensors 15 cm apart and a silver-silver chloride cutaneous reference electrode (Digitrapper Marc III, Medtronic Synectics, Maastricht, The Netherlands). Only this probe is offered in the authors’ country because, given the length in the Turkish population, it is accepted as the most appropriate one to obtain pH values close to or at the level of the UES. Before beginning the study, both probes were calibrated simultaneously in buffer solutions of pH 1 and pH 7. The distal probe was placed 5 cm above the proximal border of the lower esophageal sphincter. A lateral chest radiograph confirmed the position. The proximal probe was positioned 15 cm proximal to the distal probe. It was recommended that all patients eat their regular meals without any restriction. Meal periods and events during a 120-minute postprandial period were deleted from analysis. Acid exposure time (percentage of the study time for which the pH value was 4 or less) and the number of reflux episodes with pH value of less than 4 (recorded from the proximal probe) were evaluated for the diagnosis of LPR. Except one, all patients included in the present study had 0.1% or more of the total time at pH below 4, as well as more than five reflux episodes, exceeding acid exposure time and number of reflux episodes reported in normal healthy subjects.9,10 One patient who had 0% of the total time at pH below 4 with two reflux episodes was not excluded because this patient complained of all the typical symptoms of
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Fig. 1. Electrophysiological recordings during swallowing event. The electrophysiological measurements associated with submental electromyographic (SM-EMG) and cricopharyngeal electromyographic (CP-EMG) recordings were as follows: 1) the peak SM-EMG amplitude and its duration (from baseline to B and AC); 2) the duration of CP pause (2); 3) the duration of foreburst and the rising time of rebound burst (1 and 3); and 4) peak amplitudes of the foreburst and rebound burst (from baseline to 4 and 5).
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compared with those of 20 healthy volunteers without any neurological or laryngological symptoms and signs. The normal upper and lower limits for the durations were set at mean value ⫾ 2 SD of the measurements in healthy subjects whose ages did not significantly differ from the patients (healthy subjects: age range, 29 – 61 y; mean age, 44.3 ⫾ 10 y [P ⫽ .52]). Because of the great variability of the amplitudes, only the absence of the foreburst and the rebound burst was taken into consideration to determine the abnormality. The frequency of the foreburst and rebound burst observed in the patient group was compared with that of the healthy group, using Fisher’s Exact test. Among recorded forebursts and rebound bursts in each patient, the longest one was chosen for statistical evaluation. In addition, the mean of the peak amplitudes, the ratio of the observed forebursts and rebound bursts during the repeated swallowing events, and the percentage of the foreburst amplitude to the rebound burst amplitude in each patient were calculated to study the correlation with acid exposure time and number of reflux episodes. All electrophysiological measurements of the patients were compared with acid exposure time (percentage of the study time during which the pH value was 4 or less) and the number of reflux episodes using Spearman’s correlation test.
RESULTS In all patients, the durations of SM-EMG, CP pause, and foreburst and the rising time of rebound burst were between lower and upper limits of the normal range (Table II). The SM-EMG always started before CP pause. Foreburst was recorded in 18 of 20 patients during at least one of the repeated swallowing events, whereas it occurred in 13 of 20 healthy subjects. The difference was not statistically significant (P ⫽ .13). The higher frequency of foreburst in the patient group than that in healthy group implied that foreburst, even if of shorter minimum duration but still within normal limits, could occur more easily in patients with LPR. Figure 2 shows a patient with absent foreburst. Rebound burst was detected in all patients during all swallowing events, as well as in healthy subjects. The correlation coefficient and P values of electrophysiological parameters compared with acid exposure time and number of reflux episodes are shown in Table III. Only the durations of foreburst revealed significant correlation with the number of reflux episodes and acid exposure time. The correlation with the number of reflux episodes was good. The foreburst duration increased with the increasing number of reflux episodes. The regression lines
Fig. 2. Recording from patient 6 with absent foreburst.
are shown in Figure 3. Age of the patients did not correlate with the number of reflux episodes and acid exposure time (P ⫽ .13 and P ⫽ .07, respectively).
DISCUSSION Cricopharyngeal muscle function has been evaluated in earlier studies in patient groups with dysphagia and without a neurological disease, and GER has been found as one of the associated syndromes on endoscopy.8 Studies evaluating CP muscle by barium fluoroscopy or cineradiography in patients with GER revealed that incoordination and premature contraction of the CP muscle correlated with GER.12 In our study in patients with LPR, an electrophysiological abnormality of CP muscle and of the timing of activation of SM and CP muscles was not detected. All of the electrophysiological measurements in our patients were within normal limits. The continuous CP muscle activity is suggested to account in part for the UES pressure. Cessation of the electrical activity in CP muscle causes a marked reduction in the resting pressure of UES.5 During sleep the resting pressure of UES decreases significantly. This decrease may provide a favorable condition for esophagopharyngeal reflux.6 However, the UES resting pressure was not significantly different among normal volunteers, in posterior laryngitis, and in patients with GER.6 Correspondingly,
TABLE II. Electrophysiological Measurements Obtained in 20 Laryngopharyngeal Reflux Patients and 20 Healthy Subjects. Mean ⫾ SD (Range) Measurement
Submental EMG duration Cricopharyngeal EMG pause Foreburst duration* Rebound burst duration
Laryngopharyngeal Reflux Patients
Healthy Subjects
1030.5 ⫾ 192.8 (720–1400) 505.3 ⫾ 104.7 (308–662) 186.4 ⫾ 77.9 (80–380) 188 ⫾ 91.9 (75–407)
898.6 ⫾ 132.5 (650–1288) 451.2 ⫾ 97.7 (300–630) 254.9 ⫾ 86.4 (132–408) 256.2 ⫾ 103.5 (52–406)
* In the patient group, as well as in the healthy group, mean value of the foreburst duration was calculated including cases in which foreburst occurred at least once during repeated swallowing events. Cases in which foreburst never occurred were not included. EMG ⫽ electromyographic.
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TABLE III. Correlation Coefficients and P Value of Correlations of Electrophysiological Data and Acid Exposure Time and Number of Reflux Episodes. Acid Exposure Time
Electrophysiological parameters
Duration of SM-EMG (ms) Amplitude of SM-EMG (V) Cp-pause (ms) Foreburst duration (ms) Foreburst amplitude (V) Occurrence of foreburst (%) Rebound rising phase (ms) Rebound amplitude (V) Foreburst/rebound amplitude† (%)
No. of Reflux Episodes
Mean ⫾ SD (Range)
Correlation Coefficient
Significance (2-Tailed)
Correlation Coefficient
Significance (2-Tailed)
1030.5 ⫾ 192.78 (720–1400) 204.14 ⫾ 54.9 (125–333.4) 505.34 ⫾ 104.7 (308–662.5) 186.4 ⫾ 77.9 (80–380) 99.4 ⫾ 67.7 (20–278.8) 65.5 ⫾ 36.1 (0–100) 188.2 ⫾ 91.9 (75–407) 221.7 ⫾ 109 (93.3–⫺480) 43.1 ⫾ 36.4 (0–114.3)
0.19 ⫺0.12 ⫺0.11 0.48 0.23 0.19 ⫺0.05 0.1 0.03
0.43 0.62 0.64 0.044* 0.36 0.43 0.85 0.7 0.92
0.15 ⫺0.18 ⫺0.25 0.52 0.31 0.09 ⫺0.03 0.33 ⫺0.05
0.52 0.45 0.3 0.026* 0.21 0.7 0.91 0.16 0.84
*Correlation was significant (two-tailed). †Foreburst/rebound amplitude: percentage of foreburst amplitude to rebound burst amplitude. SM-EMG ⫽ submental electromyography.
our study did not reveal any abnormality of the tonic activity of CP muscle. A number of protective reflexes between upper gastrointestinal and upper airway tracts that affect UES function have been documented. In patients with LPR the thresholds of laryngeal adductor reflex and the pharyngeal-UES contractile reflex were impaired.13,14 It has been suggested that pharyngeal-UES contractile reflex was activated during pharyngeal reflux of gastric and/or esophageal content, thus increasing the UES pressure and possibly preventing further entry of the refluxate into the pharynx.14 Probably corresponding to these re-
sults, the main finding of our study, the positive correlation of the foreburst duration with the number of reflux episodes and acid exposure time, suggested the same mechanism. Moreover, the higher frequency of recorded forebursts in patients than in healthy subjects, although not statistically significant, supported the previous finding and could be considered as another indicator of increased reflex response. The foreburst is suggested to be a kind of protective reflex strictly related to oropharyngeal function, whereas the rebound activity is an electrical event strictly bounded by the sequential muscle activity of the central pattern generator at the brainstem.15 Similar reflex responses are observed in the EMG of the laryngeal adductor muscles during swallowing as an oral-laryngeal reflex preceding the excitation of laryngeal adductors for closure of the larynx.16 The duration of the foreburst correlating with acid exposure time and number of reflux episodes in our study supported the opinion that foreburst is a protective oropharyngeal reflex and its duration increased to prevent laryngopharyngeal structures from acid reflux.
CONCLUSION Cricopharyngeal muscle electrophysiology is normal in patients with LPR. The duration of the foreburst correlating with acid exposure time and number of reflux episodes suggested that foreburst duration increased because of the irritation caused by the acid reflux.
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Fig. 3. Regression line of foreburst duration with (A) the number of reflux episodes and (B) acid exposure time.
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