Prolonged Swallowing Time in Dysphagic Parkinsonism Patients With ...

2080

ORIGINAL ARTICLE

Prolonged Swallowing Time in Dysphagic Parkinsonism Patients With Aspiration Pneumonia Chia-Wei Lin, MD, Yeun-Chung Chang, MD, Wen-Shiang Chen, MD, PhD, Kevin Chang, MD, Hui-Ya Chang, MS, SLP, Tyng-Guey Wang, MD ABSTRACT. Lin C-W, Chang Y-C, Chen W-S, Chang K, Chang H-Y, Wang T-G. Prolonged swallowing time in dysphagic Parkinsonism patients with aspiration pneumonia. Arch Phys Med Rehabil 2012;93:2080-4. Objective: To quantitatively measure which dysphagic features, including swallowing time and hyoid bone displacement, would be associated with increased risk of aspiration pneumonia in dysphagic Parkinsonism patients. Design: Clinical survey. Setting: Tertiary care center. Participants: Patients with Parkinsonism and dysphagia (N⫽25), referred for videofluoroscopic swallowing study, were recruited by retrospective review of medical records. They were divided into 2 groups according to the history of aspiration pneumonia. Interventions: Not applicable. Main Outcome Measure: Swallowing time including onset of pharyngeal swallowing, oral transit time and pharyngeal transit time, and maximum hyoid bone displacement including total, horizontal, and vertical displacement during swallowing in thin and thick bariums were recorded. Results: Patients with history of aspiration pneumonia had significantly longer pharyngeal transit time (4.14 vs 2.31s, P⫽.038) and onset of pharyngeal swallowing (2.16 vs 1.04s, P⫽.031) than those without, when swallowing thin barium. Patients with aspiration pneumonia also had significantly longer swallowing time when swallowing thick barium (oral transit time: 7.14 vs 2.33s, P⫽.018; pharyngeal transit time: 6.39 vs 1.23s, P⫽.004; onset of pharyngeal swallowing: 5.11 vs .31s, P⫽.006). There was no significant difference in hyoid bone displacement between the 2 groups. Conclusions: Patients with Parkinsonism dysphagia and aspiration pneumonia had longer swallowing time than those without, but there was no difference in displacement of hyoid bone. Key Words: Deglutition disorders; Movement disorders; Parkinsonian disorders; Rehabilitation. © 2012 by the American Congress of Rehabilitation Medicine

YSPHAGIA IS COMMON in patients with ParkinsonD ism. In severe cases, it can lead to aspiration pneumonia and even cause mortality. Aspiration pneumonia remains the 1,2

leading cause of death in patients with Parkinsonism.3-8 Parkinsonism can be classified as Parkinson’s disease, secondary Parkinsonism (related to drug, infection, or vascular lesion), and other neurodegenerative Parkinsonism (eg, progressive supranuclear palsy, multiple system atrophy), which share common features with bradykinesia, resting tremor, rigidity, and postural instabilities.9-11 Parkinson1 first reported that patients with Parkinsonism had difficulty initiating swallowing, self-feeding, had impaired oral containment of saliva and food, and suffered from labored lingual movements. The clinical features of a swallowing disorder in Parkinsonism were expanded through radiologic studies, especially videofluoroscopic swallowing studies (VFSSs). Longer premotor transit time and multiple prepharyngeal motor abnormalities considered secondary to disease-related bradykinesia and rigidity were reported.12,13 Abnormalities in the pharyngeal phase include slowed pharyngeal constriction, slowed laryngeal elevation, increased pharyngeal and pyriform sinus retention, and laryngeal penetration or aspiration.14-16 Leopold and Kagel12 reported that patients with Parkinsonism have deficient epiglottic positioning, deficient epiglottic range of motion, and a slowed return to the preswallow resting position. Esophageal abnormalities included cricopharyngeal sphincter abnormalities,12,15,17 delayed transport, stasis, and bolus redirection.12 The consistency of food also influences swallowing ability. Parkinsonism patients had longer oral transit time (OTT), increased tongue pumping, and lower penetration-aspiration scores for pudding-thick consistency than for thin consistency.18 Although several articles have reported on features of dysphagia in Parkinsonism patients, few have discussed the relationship between these features and risk of aspiration pneumonia. In addition, there are limited reports of quantitative measurement of swallowing function in Parkinsonism patients. Therefore, the aim of our study was to quantitatively measure which dysphagic features, including swallowing time and hyoid bone displacement, would be associated with increased risk of aspiration pneumonia in dysphagic Parkinsonism patients. METHODS

From the Departments of Physical Medicine and Rehabilitation (Lin, Chen, K. Chang, Wang) and Medical Imaging (Y.C. Chang), National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei; and the National Taipei College of Nursing, Taipei (H.Y. Chang), Taiwan, R.O.C. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Correspondence to Tyng-Guey Wang, MD, No 7, Chung Shan S Rd, Taipei 100, Taiwan, e-mail: [email protected]. Reprints are not available from the author. In-press corrected proof published online on Sep 19, 2012, at www.archives-pmr.org. 0003-9993/12/9311-00582$36.00/0 http://dx.doi.org/10.1016/j.apmr.2012.07.010

Arch Phys Med Rehabil Vol 93, November 2012

Participants We retrospectively reviewed the medical records of a tertiary teaching university hospital from 2002 to 2010. We included

List of Abbreviations OPS OTT PTT VFSS

onset of pharyngeal swallowing oral transit time pharyngeal transit time videofluoroscopic swallowing study

PROLONGED SWALLOW IN PARKINSON DYSPHAGIA, Lin

Parkinsonism patients with dysphagia, who were referred for VFSSs. Dysphagia is defined if the patients subjectively have difficulties in swallowing, including choking during a meal, food stuck in the throat, unable to swallow, and markedly prolonged meal time. The decisions of referral for the VFSSs were made by the physicians, who specialize in the fields of movement disorders and dysphagia. The major referred reasons through chart review were coughing/choking during meal, difficulty in swallowing, reduced intake or weight loss, and frequent fever with profound sputum. Patients who had stroke, dementia, or other neurologic disorders, such as motor neuron diseases, were excluded. Twenty-five patients were recruited. The disease entities were idiopathic Parkinson’s disease, progressive supranuclear palsy, and Parkinson variant of multiple system atrophy. We divided the patients into 2 groups: 17 had a history of aspiration pneumonia and 8 had no history of aspiration pneumonia. Aspiration pneumonia was diagnosed with the following features: the history of choking during a meal, fever with elevated white counts, abnormal breathing sounds, abnormal radiograph findings, and no previous lung disease history. All of the patients had received clinical assessments from the neurology outpatient clinics, including disease severity according to the Hoehn and Yahr stage, and had taken anti-Parkinsonism medications (eg, levodopa/carbidopa, selegiline, amantadine). No patients had received deep brain stimulation. The university hospital ethical board approved the study. Videofluoroscopic Swallowing Study VFSS had been extensively performed in our institute. Standardized VFSS was performed by using a remote-controlled fluoroscopea equipped with a high resolution super-VHS recorder (BR 1200b). The videotape recorder had a frame rate of 30 frames per second and could display real-time dynamic images and frame-by-frame static images. The patients sat on a customized chair (VFES chairc) with a headrest to control the head posture of the subjects in a fixed distance to the videotape recorder. Each patient swallowed standardized formula of barium sulfate (E-Z HDd), which was 5mL thin barium and 5mL thick barium. The thin barium sulfate consisted of a suspension of 340g of E-Z HD and 65mL of water. The thick barium was prepared by adding extra 7.5mL of E-Z HD powder to 15mL of the standard thin barium preparation. VFSS Analysis Temporal measures. OTT was measured from the first backward movement of the bolus until the head of the bolus passed the point where the ramus of the mandible crosses the base of the tongue. Pharyngeal transit time (PTT) was measured from the time the head of the bolus passed the ramus of the mandible until the tail of the bolus left the cricopharyngeal region. Onset of pharyngeal swallowing (OPS) was measured from when the head of the bolus passed the ramus of the mandible until the onset of laryngeal elevation. OTT, PTT, and OPS were measured by a single radiologist with 20 years of experience in reading VFSS images.19 Displacement Measures Displacement of hyoid bone was studied by a physician trained in the rehabilitation department for 2 years, and a speech pathologist who had 1 year of experience reading VFSS images. Both examiners were blinded to the patient history of aspiration pneumonia. The lateral views of the fluoroscopic images were recorded digitally at 30 frames per second in Moving Picture Experts Group format. The series of frames

2081

Fig 1. Quantitative measurement of hyoid bone movement in VFSS: the line between the anterior inferior angle of the C3 and C4 vertebral body was defined as the y-axis, and the x-axis was defined as the line crossing the anterior inferior angle of C4, and 90° vertical to the y-axis. Point A represents the origin (0,0), which was defined at the anterior inferior angle of the C4 vertebral body. Point B represents the anterior inferior angle of the hyoid bone. Distance CD represents the length of radiopaque paper clip.

were identified and saved as bitmap picture files using Premiere Pro (version 2.0e).e A self-designed program written in MATLAB (R2007bf)f was used to analyze individual frames. This program assessed horizontal and vertical displacement of the hyoid bone, and total hyoid bone movement during swallowing. Coordinates in each frame were defined as follows: (1) the line between the anterior inferior angle of the C3 and C4 vertebral body was defined as the y-axis, and the x-axis was defined as the line crossing the anterior inferior angle of C4 and 90° vertical to y-axis; (2) the origin (0,0) was defined at the anterior inferior angle of C4 vertebral body; and (3) the position of anterior inferior angle of hyoid bone was recorded as (X,Y). This coordinate system simplified the vertical and horizontal displacement of the hyoid bone and assured that the calculation was relative to the vertebral column. A 2.5-cm-long radiopaque paper clip taped on the left lower side of the fluoroscopic screen was used to calibrate the digitized image (fig 1). The self-designed program analyzed the maximum values during the trajectory. Rater Reliability To test for interrater and intrarater reliability of measuring hyoid bone displacement, 5 participants were randomly chosen for reanalysis. Statistics Data were analyzed using the Statistic Package for Social Sciences (SPSS) 17 softwareg for Windows. Chi-square test was used to test hypotheses regarding categorical variables. Preliminary statistics for each variable were performed to determine the normality of distribution (Shapiro-Wilk test). Mann-Whitney U test was used for analysis of the nonnormal distribution of temporal parameters (ie, OTT, PTT, and OPS) between Parkinsonism patients with or without history of aspiration pneumonia. Independent t test was used for analysis of Arch Phys Med Rehabil Vol 93, November 2012

2082

PROLONGED SWALLOW IN PARKINSON DYSPHAGIA, Lin Table 3: Hyoid Bone Displacement in Parkinsonism Patients With or Without History of Aspiration Pneumonia

Table 1: Demographic Characteristics of Participants

Characteristics

With History of Aspiration Pneumonia (n⫽17)

Without History of Aspiration Pneumonia (n⫽8)

Sex (male/female) Age (y) Hoehn-Yahr stage I II III IV V

13/4 75.4⫾6.6 3.7⫾0.5 0 0 5 11 1

6/2 74.0⫾8.9 3.0⫾1.1 1 2 1 4 0

P

.936* .758† .119‡

*Chi-square test. Student t test. ‡ Mann-Whitney U test.

the normal distribution of hyoid bone displacement between Parkinsonism patients with or without history of aspiration pneumonia. Intraclass correlation was used to test the intra-and interrater reliability of the studied parameters. A P value of ⬍.05 was taken as significant difference. RESULTS There was no difference in age, sex, and disease severity (according to Hoehn and Yahr stage) in patients with Parkinsonism dysphagia with or without history of aspiration pneumonia (table 1). Patients with a history of aspiration pneumonia had significantly longer PTT (4.14⫾1.36s vs 2.31⫾1.99s, P⫽.038) and OPS (2.16⫾1.47s vs 1.04⫾1.95s, P⫽.031) than those without such history while swallowing thin barium, but the OTT was the same between the 2 groups. Patients with a history of aspiration pneumonia had significantly longer OTT, (7.14⫾12.99s vs 2.33⫾2.54s, P⫽.018), PTT (6.39⫾12.93s vs 1.23⫾.43s, P⫽.004), and OPS (5.11⫾13s vs .31⫾.23s, P⫽.006) than those without such history while swallowing thick barium (table 2). There was no significant difference in hyoid bone displacement, including total, vertical, and horizontal displacement, with both thin and thick bariums, between aspiration pneumonia and nonaspiration pneumonia groups (table 3). The intrarater, intraclass correlation coefficient of hyoid bone displacement ranged from .51 to .88. The interrater, intraclass correlation coefficient of hyoid bone displacement was between .53 and .90. Table 2: Swallowing Time of Parkinsonism Patients With or Without History of Aspiration Pneumonia

Swallowing Time

Thin barium OTT (s) PTT* (s) OPS (s) Thick barium OTT (s) PTT* (s) OPS (s)

Thin barium Horizontal displacement (cm) Vertical displacement (cm) Total displacement (cm) Thick barium Horizontal displacement (cm) Vertical displacement (cm) Total displacement (cm)

P

2.0⫾0.75 2.84⫾0.98 2.39⫾0.88

1.78⫾0.83 2.34⫾1.02 2.01⫾1.13

.972 .487 .373

1.86⫾0.50 2.92⫾0.90 2.29⫾0.72

2.13⫾1.10 2.54⫾1.01 2.35⫾1.28

.821 .528 .909

NOTES. Independent t test was used. Values are mean ⫾ SD.

†

With History of Aspiration Pneumonia (n⫽17)

Hyoid Bone Displacement

With History Without History of Aspiration of Aspiration Pneumonia Pneumonia (n⫽17) (n⫽8)

Without History of Aspiration Pneumonia (n⫽8)

P

3.84⫾2.14 4.14⫾1.36 2.16⫾1.47

2.51⫾2.83 2.31⫾1.99 1.04⫾1.95

.098 .038 .031

7.14⫾12.99 6.39⫾12.93 5.11⫾13.00

2.33⫾2.54 1.23⫾0.43 0.31⫾0.23

.018 .004 .006

NOTES. Mann-Whitney U test was used. Values are mean ⫾ SD. *Three patients failed in swallowing barium into the esophagus, and therefore PTT could not be calculated.


DISCUSSION This study shows that dysphagia in Parkinsonism patients with aspiration pneumonia may be associated with prolonged swallowing time rather than displacement of hyoid bone. Safe swallowing depends on good airway protection20-23 and adequate hyolaryngeal elevation,24,25 which is correctly timed. In-time hyolaryngeal elevation depends on an intact swallowing response, involving normal sensation, reflex arch, brain center, and target muscles.20-23 Adequate hyoid elevation requires intact suprahyoid muscles movements.26,27 In this study, OPS was significantly longer in the aspiration pneumonia group than in the group without aspiration pneumonia. The prolonged OPS indicated delayed closure of the airway during swallowing. Hyoid bone displacement was similar between the 2 groups, indicating that hyoid elevation was similar. On this basis, our study discloses that the cause of aspiration pneumonia among patients with Parkinsonism dysphagia was probably delayed swallowing response rather than impaired laryngeal elevation. Therefore, for prevention of aspiration pneumonia in this group, the timely initiation of the pharyngeal events of swallow is crucial. Previous studies have also reported delayed OPS in Parkinsonism patients28,29; however, the mechanism remains unknown. The medullary central pattern generators are located in the medial reticular formation of the rostral medulla and in the reticular formation adjacent to the nucleus tractus solitarius. The central pattern generators project to the nucleus ambiguous, which innervates the striated muscles of the pharynx, larynx, and esophagus, and also project to dorsal motor nucleus of the vagus, to control esophageal contraction.30 Hence, the delayed OPS in patients with Parkinsonism dysphagia may be from abnormal basal ganglionic suprasegmental control of medullary function, although there is insufficient neurophysiologic evidence to support this. In addition to medullary central pattern generators, Alfonsi et al31 suggested that degeneration of cholinergic neurons in pedunculopontine tegmental nucleus, which receive projections from the substantia nigra pars reticulata, may affect initiation, modulating, and timing of the swallowing response in Parkinsonism patients, especially in patients with Parkinson’s disease, progressive supranuclear palsy, and Parkinson variant of multiple system atrophy. The present study also shows that patients with Parkinsonism dysphagia and a history of aspiration pneumonia had longer OTT than those without such history, when swallowing thick but not thin barium. OTT usually indicates the power and efficiency of tongue movement. Parkinsonism patients have longer OTT while swallowing thin barium, compared with young or older healthy control adults.32 The prolonged OTT


may be because of rigidity, bradykinesia of tongue movement, and increased tongue pumping.16,33 Thicker consistencies of food, which need more efficient muscle power to propel the bolus, predictably lead to longer OTT.34 This may imply that Parkinsonism patients have impaired tongue movements that are more severe in those with a history of aspiration pneumonia. PTT was longer in the Parkinsonism patients with history of aspiration pneumonia than in those without. Previous reports of PTT in Parkinsonism patients have varied. Nagaya et al32 reported that Parkinsonism patients did not have longer PTT while swallowing thick barium, compared with controls. But some studies reported prolonged PTT, assessed by VFSSs29 or submental surface electromyography studies.28,35 Prolonged PTT may be related to delay of OPS, slow pharyngeal constriction,12 or possible impairment of upper esophagus relaxation.36 This impairment might be caused by degeneration of the dorsal motor nucleus of the vagus nerve37 or the esophageal myenteric plexus.36 There are limited quantitative studies of hyoid bone displacement during swallowing in Parkinsonism patients. Our study showed no difference in hyoid bone displacement between Parkinsonism patients with or without history of aspiration pneumonia. Leonard et al38 found that in healthy adults, maximum hyoid bone displacement was 1.86⫾0.6cm and 2.16⫾.85cm while swallowing 3 and 20cc of thin barium, respectively. Hyoid bone displacement in our study was 2.39 and 2.01cm in patients with and without history of aspiration pneumonia, respectively, which is similar to that of healthy adults. Troche et al39 reported that hyoid bone displacement increased from 1.13 to 1.15cm (P⫽.009), and the penetrationaspiration score decreased from 2.65 to 2.07 (P⫽.021) after expiratory muscle strength training in Parkinsonism patients. In their study, hyoid bone displacement was much less than in other reports. The improvement in hyoid bone displacement and in penetration-aspiration scores after treatment was small, and the patients selected only had mild swallowing abnormalities. Stelmach and Worringham40 reported that there were no apparent weakness of limb muscles in Parkinsonism patients in the isometric muscle strength test, but a longer time to reach peak torque and contraction duration was required. This implies that Parkinsonism patients have deficiency in the regulation of force and time parameters rather than simply in force production. Their result might explain why the Parkinsonism patients had the same displacement of hyoid bone but delayed laryngeal elevation and implies that weakness in suprahyoid muscles may not be a leading cause of aspiration pneumonia in Parkinsonism patients with severe dysphagia. Study Limitations There are several limitations to this study. First, the case numbers were limited, and most patients were in late stages of Parkinsonism. Also, participants were those referred for the VFSS study with highly suspected aspiration or severe dysphagia, which might limit the applicability to all dysphagic Parkinsonism patients. Besides, the small sample size may have limited the statistical power to detect significant changes in some parameters, such as hyoid displacement. However, the aim was to study the probable risk parameters for aspiration pneumonia in dysphagic Parkinsonism patients. The results may at least in part establish the association of prolonged swallowing time and increased risk of aspiration pneumonia in dysphagic Parkinsonism patients. Second, this study did not focus on comparing the doses, varieties, or on-off phenomenon of medications41 during VFSS studies, although the patients enrolled were all taking anti-Parkinsonism medications. Previ-

2083

ous studies pointed out that dopaminergic agents mainly influence the oral stage and have little effect in the pharyngeal stage.42 Lim et al41 also pointed out that there is no difference in average time per swallow between on and off states. Hence, the efficacy of medications may not have affected the results of the study. Third, the study populations are Parkinsonism patients, which include patients of Parkinson’s disease, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy. Although multiple system atrophy is considered to have additional involvement of the brainstem, which may contribute to dysphagia in Parkinsonism,43,44 the previous electrophysiologic study disclosed that these Parkinsonism syndromes inherit bradykinesia as a common swallowing abnormality.31 Hence, our study implies that these Parkinsonism syndromes may share some common features of dysphagia. A more comprehensive prospective study design with larger numbers of patients is needed. Furthermore, studies could be done to determine to what magnitude of delay of swallowing time leads to aspiration pneumonia in patients with Parkinsonism dysphagia. We could also study the effect of facilitating swallowing response in prevention of aspiration pneumonia in these patients. CONCLUSIONS Patients with Parkinsonism dysphagia with history of aspiration pneumonia had longer PTT and OPS than patients without, although hyoid bone displacement was the same for both groups. Hence, the cause of aspiration pneumonia in patients with Parkinsonism dysphagia may be associated with prolonged swallowing time rather than inadequate laryngeal elevation. References 1. Parkinson J. An essay on the shaking palsy. London: Whittingham and Bowland; 1817. 2. Penner A, Druckerman LJ. Segmental spasms of the esophagus and their relation to Parkinsonism. Am J Digest Dis 1942;9: 272-86. 3. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;17:427-42. 4. Singer RB. Mortality in patients with Parkinsons disease treated with dopa. J Insur Med 1992;24:126-7. 5. Gorell JM, Johnson CC, Rybicki BA. Parkinsons disease and its comorbid disorders: an analysis of Michigan mortality data, 1970 to 1990. Neurology 1994;44:1856-8. 6. Shill H, Stacy M. Respiratory function in Parkinsons disease. Clin Neurosci N Y 1998;5:131-5. 7. Schiermeier S, Schäfer D, Schäfer T, Greulich W, Schläfke ME. Breathing and locomotion in patients with Parkinsons disease. Pflugers Arch 2001;443:67-71. 8. Fernandez HH, Lapane KL. Predictors of mortality among nursing home residents with a diagnosis of Parkinson’s disease. Med Sci Monit 2002;8:CR241-6. 9. Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008;79:368-76. 10. Lees AJ, Hardy J, Revesz T. Parkinson’s disease. Lancet 2009; 373:2055-66. 11. Christine CW, Aminoff MJ. Clinical differentiation of parkinsonian syndromes: prognostic and therapeutic relevance. Am J Med 2004;117:412-9. 12. Leopold NA, Kagel MC. Pharyngo-esophageal dysphagia in Parkinson’s disease. Dysphagia 1997;12:11-8; discussion 9-20. 13. Nagaya M, Kachi T, Yamada T. Effect of swallowing training on swallowing disorders in Parkinson’s disease. Scand J Rehabil Med 2000;32:11-5. Arch Phys Med Rehabil Vol 93, November 2012

2084


14. Logemann JA, Blonsky ER, Boshes B. Editorial: dysphagia in parkinsonism. JAMA 1975;231:69-70. 15. Robbins JA, Logemann JA, Kirshner HS. Swallowing and speech production in Parkinson’s disease. Ann Neurol 1986;19:283-7. 16. Bushmann M, Dobmeyer SM, Leeker L, Perlmutter JS. Swallowing abnormalities and their response to treatment in Parkinson’s disease. Neurology 1989;39:1309-14. 17. Eadie MJ, Tyrer JH. Radiological abnormalities of the upper part of the alimentary tract in Parkinsonism. Australas Ann Med 1965; 14:23-7. 18. Troche MS, Sapienza CM, Rosenbek JC. Effects of bolus consistency on timing and safety of swallow in patients with Parkinson’s disease. Dysphagia 2008;23:26-32. 19. Wang TG, Wu MC, Chang YC, Hsiao TY, Lien IN. The effect of nasogastric tubes on swallowing function in persons with dysphagia following stroke. Arch Phys Med Rehabil 2006;87:1270-3. 20. Ardran GM, Kemp FH. The mechanism of swallowing. Proc R Soc Med 1951;44:1038-40. 21. Bosma JF. Deglutition: pharyngeal stage. Physiol Rev 1957;37: 275-300. 22. Ardran GM, Kemp FH. The protection of the laryngeal airway during swallowing. Br J Radiol 1952;25:406-16. 23. Ohmae Y, Logemann JA, Kaiser P, Hanson DG, Kahrilas PJ. Timing of glottic closure during normal swallow. Head Neck 1995;17:394-402. 24. Shaker R, Dodds WJ, Dantas RO, Hogan WJ, Arndorfer RC. Coordination of deglutitive glottic closure with oropharyngeal swallowing. Gastroenterology 1990;98:1478-84. 25. Zamir Z, Ren J, Hogan WJ, Shaker R. Coordination of deglutitive vocal cord closure and oral-pharyngeal swallowing events in the elderly. Eur J Gastroenterol Hepatol 1996;8:425-9. 26. Donner MW, Bosma JF, Robertson DL. Anatomy and physiology of the pharynx. Gastrointest Radiol 1985;10:196-212. 27. Jacob P, Kahrilas PJ, Logemann JA, Shah V, Ha T. Upper esophageal sphincter opening and modulation during swallowing. Gastroenterology 1989;97:1469-78. 28. Ertekin C, Tarlaci S, Aydogdu I, et al. Electrophysiological evaluation of pharyngeal phase of swallowing in patients with Parkinson’s disease. Mov Disord 2002;17:942-9. 29. Stroudley J, Walsh M. Radiological assessment of dysphagia in Parkinson’s disease. Br J Radiol 1991;64:890-3. 30. Miller AJ. Neurophysiological basis of swallowing. Dysphagia 1986;1:91-100. 31. Alfonsi E, Versino M, Merlo IM, et al. Electrophysiologic patterns of oral-pharyngeal swallowing in parkinsonian syndromes. Neurology 2007;68:583-9. 32. Nagaya M, Kachi T, Yamada T, Igata A. Videofluorographic study of swallowing in Parkinson’s disease. Dysphagia 1998;13: 95-100.


33. Edwards LL, Quigley EM, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease: frequency and pathophysiology. Neurology 1992;42:726-32. 34. Dantas RO, Dodds WJ. Effect of bolus volume and consistency on swallow-induced submental and infrahyoid electromyographic activity. Braz J Med Biol Res 1990;23:37-44. 35. Ali GN, Wallace KL, Schwartz R, DeCarle DJ, Zagami AS, Cook IJ. Mechanisms of oral-pharyngeal dysphagia in patients with Parkinson’s disease. Gastroenterology 1996;110:383-92. 36. Sung HY, Kim JS, Lee KS, et al. The prevalence and patterns of pharyngoesophageal dysmotility in patients with early stage Parkinson’s disease. Mov Disord 2010;25:2361-8. 37. Jellinger K. Overview of morphological changes in Parkinson’s disease. Adv Neurol 1987;45:1-18. 38. Leonard RJ, Kendall KA, McKenzie S, Goncalves MI, Walker A. Structural displacements in normal swallowing: a videofluoroscopic study. Dysphagia 2000;15:146-52. 39. Troche MS, Okun MS, Rosenbek JC, et al. Aspiration and swallowing in Parkinson disease and rehabilitation with EMST: a randomized trial. Neurology 2010;75:1912-9. 40. Stelmach GE, Worringham CJ. The preparation and production of isometric force in Parkinson’s disease. Neuropsychologia 1988; 26:93-103. 41. Lim A, Leow L, Huckabee ML, Frampton C, Anderson T. A pilot study of respiration and swallowing integration in Parkinson’s disease: “on” and “off” levodopa. Dysphagia 2008;23:76-81. 42. Baijens LW, Speyer R. Effects of therapy for dysphagia in Parkinson’s disease: systematic review. Dysphagia 2009;24:91-102. 43. Benarroch EE, Schmeichel AM, Sandroni P, Low PA, Parisi JE. Involvement of vagal autonomic nuclei in multiple system atrophy and Lewy body disease. Neurology 2006;66:378-83. 44. Papp MI, Lantos PL. The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain 1994;117:235-43. Suppliers a. Medix; Hitachi Medical Corp, 7 Kanda Mitoshirocho, Chiyodaku, Tokyo 101-0053, Japan. b. Victor Co of Japan, 3-12 Moriya-Cho, Kanagawaku, Yokohama 221-8528, Japan. c. Vess Chairs Inc, 12201 W North Ave, Ste 107-110, Wautwatosa, WI 53226. d. E-Z-EM Inc, 1111 Marcus Ave, Suite LL26, Lake Success, NY 11042. e. Adobe Systems Inc, 345 Park Ave, San Jose, CA 95110-2704. f. The MathWorks Inc, 3 Apple Hill Dr, Natick, MA 01760. g. SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606-6307.