Dysphagia 10:22-26 (1995)

Dysphagia �9 Springer-Verlag New York Inc. 1995

Manometric Characteristics of the Pharynx, Upper Esophageal Sphincter, Esophagus, and Lower Esophageal Sphincter in Patients with Oculopharyngeal Muscular Dystrophy

June A. Castell, MS, Donald O. Castell, MD, C. Andre Duranceau, MD, and Philippe Topart, MD Department of Medicine, The Graduate Hospital, Philadelphia, Pennsylvania, USA, and Department of Surgery, Universit6 de Montreal, Hotel-Dieu de Montreal Hospital, Montreal, Quebec, Canada

Abstract. Improved techniques in esophageal manome- try have made this test an attractive option for investigat- ing pharyngeal or esophageal disorders in patients with dysphagia. We studied esophageal as well as upper esophageal sphincter/pharyngeal (UES/P) pressure dy- namics in 11 patients with an established diagnosis of oculopharyngeal muscular dystrophy with modem solid- state manometric techniques and then compared mano- metric and clinical findings. Esophageal manometric ab- normalities were found in 10/11 patients, with the most common being simultaneous contractions and incomplete lower esophageal relaxation. 9/11 patients showed ab- normal UES/P manometrics, with the most common ab- normalities found in the pharynx. The presence of mano- metric abnormalities closely paralleled clinical assessment of degree o f disease severity. Modem mano- metric techniques offer an opportunity for a quantitative assessment of swallow abnormalities.

Key words: Manometry - - Oculopharyngeal - - Mus- cular dystrophy - - Deglutition disorders - - Deglutition

Oculopharyngeal muscular dystrophy (OPMD) is a rare form of muscular dystrophy. It is genetically transmitted and is an autosomal dominant. This condition, as first described by Taylor [1], is found primarily in Canadians of French descent, however, there have been some re- ports of the disease in other ethnic groups [2-4]. It is manifested by bilateral ptosis and oropharyngeal dyspha-

Address offprint requests to: June A. Castell, The Graduate Hospital, Department of Medicine, Suite 501, Pepper Pavilion, Philadelphia, PA 19146, USA

gia. The disease progresses slowly, with symptoms usu- ally appearing late in life. It is important to note, how- ever, that clinically similar cases may not all belong to the same group of diseases and it is not entirely clear whether oculopharyngeal muscular dystrophy should be separated from the classification of other ocular myopa- thies [5].

Manometric and radiographic studies in patients with OPMD have revealed evidence of pharyngeal weak- ness and/or defective relaxation of the upper esophageal sphincter (UES) [6-8]. We have recently developed the technology to provide more accurate quantitative assess- ment of pharyngeal and UES pressure dynamics [9]. In this report we describe studies using our solid state com- puterized manometric technique to evaluate swallowing dynamics in a group of patients with OPMD. Manomet- ric findings were compared to an independently scored clinical assessment o f severity.

Patients and Methods

We studied 11 patients (6 M, 5 F; mean age 61.7 years; range 50-72) with an established diagnosis of oculopharyngeal muscular dystrophy based on their clinical presentation and familial history. Over a period of 2 years they underwent clinical, radiological, and scintigraphic as- sessments, as well as complete esophageal and pharyngeal manometry.

Four patients were initially referred by a neurologist seven fam- ily physician [7]. An independent clinical assessment was performed by one of the authors (AD) and included an evaluation of digestive symp- toms such as dysphagia and regurgitation (oral and nasal); tracheo- bronchial symptoms such as persistent cough, sputum production, aspi- ration, and bronchorrhea; and peripheral muscle involvement as manifested by limb weakness, voice changes, and bilateral ptosis. Dur- ing the clinical interview, all patients were asked identical questions on the presence of pharyngo-esophageal and tracheo-bronchial symptoms. A clinical assessment score of from 0 to 3, with 3 indicating the most severe involvement, was derived from the presence, duration, and

J.A. Castell et al.: Manometric Characteristics 23

frequency of symptoms and assigned to each patient. The assessment was performed by one investigator (AD) without prior knowledge of the manometric findings.

The radiology exam was a rapid-sequence barium swallow with both AP and lateral views. Picture frames were printed at a rate of 6/sec. This exam provides adequate visualization of anatomy and function during the act of swallowing. It allows for the identification of the stage of the swallowing process during which difficulties occur and for the identification of aspiration.

The pharyngo-esophageal scintiscan measures transit time of a standard bolus through the oropharynx, hypopharynx, and esophagus, as well as aspiration and regurgitation. Data were acquired in both the sitting and the supine positions during the 3-min period following the ingestion of 10 ml water containing 1.0 mCi of 99 mTc sulfur colloid. The time necessary to clear 90% of the radioactivity for each of five segments--oropharynx, hypopharynx, proximal, mid- and distal esopha- gus was determined (along with the time to clear the entire esophagus).

The manometric exam was performed using a catheter contain- ing three solid state transducers spaced at 3-cm intervals with the most distal transducer being a circumferential sphincter transducer (Konigs- berg Inc., Pasadena CA). The sphincter transducer consists of a strain gauge surrounded by a silastic annulus filled with castor oil that is in contact with the walls of the sphincter and averages pressures over 360~ it has been previously described [9]. The lower esophageal sphincter pressure (LESP) was evaluated by the station pull-through method mad relaxation (LESR) was assessed with 5-rrd water swallows while the sphincter transducer was positioned in the high pressure zone. Esoph- ageal peristalsis was measured using six wet swallows (5 ml water) with the catheter in two locations: (1) the distal transducer was located 3 cm above the upper margin of the LES to assess distal esophageal function and (2) the proximal transducer was located 1 cm below the lower margin of the UES to assess proximal esophageal function. UES resting pressure (UESP) was measured using a slow station pull-through with 15-sec intervals for stabilization between each 1-cm movement of the catheter. Four 5-ml water swallows were used to assess UES relaxation, pharyngeal contraction, and UES/pharyngeal coordination. The swal- lows were performed with the circumferential transducer placed just proximal to the high pressure zone of the UES to allow accurate record- ing of sphincter pressures throughout the cycle of elevation of the sphincter during deglutition [10,11]. As pharyngeal pressures have been shown to be asymmetric [ 12], the transducer in the pharynx was oriented posteriorly to provide maximum contraction pressures. Mano- metric parameters were analyzed using a computerized polygraph sys- tem (Synectics Medical Inc. Dallas TX). Abnormalities were identified in three areas: (1) UES function: abnormal resting pressure, incomplete relaxation, prolonged duration of either the time to nadir or the time from nadir to recovery or both, attenuated relaxation duration; (2) pharyngeal function: low peak contraction pressure, prolonged time to peak, or time from peak to baseline or both, attenuated contraction duration; (3) incoordination: abnormal time intervals primarily between the beginning of the pharyngeal contraction and the beginning of the UES relaxation, but also between the beginning of the UES relaxation and the peak or end of the pharyngeal contraction.

Patients were assigned a manometric UES/P severity score with- out prior knowledge of their clinical assessment score. Mild involve- ment was defined as a score of 0 (no manometric abnormalities) or a score of 1 (abnormality in 1 area; either UES or P or incoordination). Severe involvement was defined as a score of 2 (abnormalities in 2 areas; UES and P, UES and incoordination, P and incoordination) or a score of 3 (abnormalities in all three areas).

Results

Frequency of swal lowing and pu lmonary symptoms are shown in Table 1. Al l patients had some degree o f dys-

Table 1. GI and pulmonary symptoms in l 10PMD patients

Occasional Frequent Total (11)

Dysphagia (solids) 3 8 11 Dysphagia (liquids) 4 2 6 Oral regurgitation 6 2 8 Nasal regurgitation 3 3 6 Cough 4 4 8 Sputum 3 4 7 Aspiration 4 3 7 Bronchorrhea 7 1 8

Table 2. Findings on esophageal manometry in 11 OPMD patients

Nontransmitted contractions 4/11 (proximal) Simultaneous contractions 9/11

(distal) Hypertensive LES 1/11

(>145 mmHg) Incomplete LES relaxation 9/11

17-83% of swallows

20-100% of swallows

33-100% of swallows

phagia , wi th dysphagia for solids being more prevalent

than dysphagia for l iquids. Oral or nasal regurgi tat ion

occurred in ove r three-fourths of the patients.

On physical exam, 10 o f the patients showed

marked bilateral ptosis; 3 had requi red prior surgical cor-

rection. W e a k speaking vo ice was detected in 7 o f the

patients. Ev idence o f musc le weakness o f the l imbs was

less c o m m o n , being present in only 3 patients.

On radiological exam, 9 o f the patients showed

some abnormal i ty o f the pharyngeal swal low, however ,

no single abnormal i ty predominated . Abnorma l relax-

ation of the U E S was descr ibed in 5 patients, wi th pha-

ryngeal stasis and aspiration in 4 and 2, respect ively .

Other f indings included ver tebral os teophytes in 2 and

abnormal esophageal peristalt ic progress ion (seen as seg-

mental contract ions on the bar ium co lumn) in 1 patient.

Retent ion on scint igraphy in dystrophic patients

was considered abnormal in relat ion to normal patients

studied in the same laboratory by the same nuclear medi-

cine physician. Scint igraphy showed some delay in pha-

ryngeal c learance i n a l l pat ients , wi th 8 showing reten-

t ion in the hypopharynx and 2 hav ing retent ion in the

oropharynx. Again , ev idence o f aspirat ion was present in

2 patients. In addit ion, 2 patients also had esophageal retention.

Esophagea l manomet ry revea led that 10 of the 11

patients had some degree o f esophageal dysfunct ion,

summar ized in Table 2. The most c o m m o n features were

s imultaneous contract ions o f the distal esophageal body and incomple te LES relaxat ions.

U E S / P manomet r i c parameters for the 11 patients are g iven in Table 3 along with normal va lues obta ined in

24 J.A. Castell et al.: Manometric Characteristics

Table 3. UES/P manometric parameters in 11 OPMD patients

UESR P BEG TO Patient UES RP DUR P dP/dT P DUR U BEG

Normal • 2 SD 7 4 • 44 - 6 • 7.3 545• 144 177 • 138 1011 • 765 402 • 246 -178 • 2t6 1 70 2 310 a 53 329 462 - 4 6 2 70 7 386 a 61 181 a 778 a 150 a 3 24 a - 4 508 128 681 441 -289 4 73 17 a 851 a 76 218 a 1015 a -360 5 62 - 3 542 265 2844 ~ 813 a -263 6 60 0 587 58 273 a 564 -146 7 65 17 a 328 a 50 142 a 815 a 229 a 8 63 0 465 267 3818 ~ 489 -252 9 41 2 641 82 155 a 1101 a 25&

10 88 1 555 229 1845 a 400 -195 11 41 - 5 480 174 94 ~ 2298 a 15753

Mean 60 3 514 131 961 834 60 SD 18 8 153 87 129l 540 547

Normal values from our laboratory ~3. UES : resting UES pressure as determined by a slow pull-through. RP = residual pressure at the nadir of the UES relaxation during deglu-

tition. UESR DUR = time interval daring the UES relaxation that the pressure remains below half resting pressure, P = peak pharyngeal pressure during the pharyngeal contraction. dP/dT = pharyngeal contraction rate (change in pressure per unit time).

P DUR = duration of the pharyngeal contraction. P BEG TO U BEG = time period from the beginning of the pharyngeal contraction to the beginning of the UES relaxation (this is nonnally a negative number, indication that the UES relaxes before the pharyngeal

contraction). aValues >2 SD from normal.

our laboratory for 14 healthy controls; the same catheter and technique were used for both groups [13]. The results of the UES/pharyngeal manometry studies are summa- rized in Table 4. Nine of the 11 patients showed abnor- mal UES/P manometrics. The most common abnormali- ties were, as expected, found in the pharynx. These were present in 6 patients and were characterized by low pha- ryngeal pressures and corresponding low pharyngeal contraction dP/dT. In addition, prolonged pharyngeal contractions and associated UES/P incoordination was found (an example is shown in Fig. 1). Abnormal UES relaxation parameters were found in 4 patients, with in- creased residual pressure in 3, and abnormal duration of relaxation in all 4- -3 short and 1 prolonged. (Fig. 2)

The UES/P mean manometric profile of the 5 patients deemed severe by clinical criteria (clinical sever- ity score of 2 or 3) was markedly abnormal (Fig. 3). In contrast, the mean UES/P manometric profile in the 6 patients classified as mild by clinical criteria (clinical severity score of 0 or 1) was normal. There was a slight positive association (p = 0.1) between the independent classification of patients into mild or severe based on clinical or manometric findings, with an odds ratio of 8. That is, patietns with severe clinical findings were 8 times more likely to have UES/P manometric abnormali- ties than patients categorized clinically mild. A type II error due to the small number of patients should be con- sidered a possibility for the failure to attain statistical significance.

Table 4. Findings on UES/P manometry in 11 OPMD patients

Abnormal UES relaxation duration High UES residual pressure Low pharyngeal pressure Low pharyngeal dP/dT Prolonged pharyngeal contraction duration UES/P incoordination

4/11 2/11 6/11 6/11 6/11 6/11

Discussion

OPMD is a rare hereditary disorder characterized by weakness of the skeletal muscle involving primarily the eyelids and the pharynx. As such, its primary clinical manifestations are ptosis and oropharyngeal dysphagia, both of which generally occur later in life and are usually progressive in nature. There have been a few studies over the years that have characterized the swallowing defect in these patients, indicating apparent weakness of the pha- ryngeal propulsive wave and possible defects in relax- ation of the UES, with or without incoordination between these two essential aspects of the pharyngeal swallow response. These studies have all been performed with mamometric techniques that are generally considered to be outdated and that have definite limitations in their ability to provide quantitative information. Our studies, using a completely solid state transducer assembly with on-line computer measurement, provides the most accu- rate quantitative studies of the pharyngeal swallow in a

J.A. Castell et al.: Manometric Characteristics 25

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Fig. 3. Schematic showing close correlation between mean UES/P values for the 11 patients categorized as mild (squares) or severe (cir- cles) using two separate criteria: clinical scores (filled) and manometric scores (open).

Fig. 1. Manometric tracing during deglutition in OPMD patient. Distal transducer (below) is measuring UES relaxation. Mid- and proximal transducers are at 3-cm intervals and are measuring pharyngeal contrac- tions. Note "M" configuration in UES transducer, indicating proper placement for measuring UES relaxation during laryngeal elevation, and complete relaxation to esophageal baseline. Pharyngeal contrac- tions are weak and prolonged (825 msec vs. 402 -+ 246 msec normal pharyngeal contraction duration at 3 cm proximal to UES).

group of patients with OPMD. We found a broad range of abnormalities in function of the pharynx and UES in the 11 patients studied. The most characteristic finding was a weakness in the contractile force in the hypopharynx with the more severe defects including incomplete relaxation of the UES. Significant elevations in the relaxation resid- ual pressure of the UES during swallowing, consistent

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Fig. 2. Manometric tracings during deglutition contrasting OPMD patient (left) with attenuated and incomplete UES relaxation (RP = 15), weak pharyngeal contractions, and incoordination to normal subject (right). Distal transducer is proximal to the high pressure zone of the UES before deglutition. Transducers are at 3-cm intervals, time scale on X axis is 0.3 sec.

26 J.A. Castell et al.: Manometric Characteristics

with a manometric diagnosis of"cricopharyngeal achaia- sia," were found in 2 of our 11 patients. This term is frequently misused in clinical medicine, being suggested either clinically in the patient who presents with transfer dysphagia of unexplained cause or with radiographic ev- idence of a hypopharyngeal bar or inability to adequately transfer a barium bolus from the hypopharynx through the UES. In the latter situation, the defect is more likely to be due to major weakness in the pharynx rather than true inadequate relaxation of the UES. This differentia- tion must be clarified with proper manometric evalua- tion. True cricopharyngeal achalasia is quite rare and has been described in OPMD and in the unusual patient with central nervous system lymphoma affecting the brain- stem [14]. Cricopharyngeal myotomy in this situation decreases the resting pressure and increases the relax- ation time of the upper esophageal sphincter area. This results in a decreased resistance to pharyngo-esophageal transit and improved pharyngeal emptying [15].

Based on the quantitative information obtained from the solid state computerized manometric studies, a severity score of the degree of pharyngeal and UES ab- normality was devised. This was shown to have a strong positive relationship with a clinical score of the severity of the patient's symptom and radiographic profile. The close association between these two independently de- rived assessments of the status of our 11 OPMD patients confirms the ability of our manometric techniques to assess the severity of the patient's swallowing defect and also suggests that manometry might be used to follow the deterioration of patients with this disease.

Another interesting aspect of the current studies was the finding of a high prevalence of abnormal motility in the smooth muscle distal esophagus. Although esoph- ageal motility defects have been reported in these pa- tients, they have not been well characterized. Abnormal distal esophageal motility, often resembling that found in diffuse esophageal spasm, should be recognized as a frequent event in patients with OPMD. It is not clear why this occurs as our understanding of the pathogenesis of this disease is primary involvement in the skeletal muscle portion of the swallowing apparatus. It is important to recognize, however, that these patients may have a com- pound swallowing disorder with both abnormal transfer in the pharyngeal swallow and also some degree of ab- normal esophageal transport.

In conclusion, modem, solid state, computerized manometric techniques allow a better quantitative assess-

ment of the degree of pharyngeal weakness in patients with OPMD and the possible defect in UES relaxation during swallowing with more severe disease. Further studies may confirm that this technique can be used to follow the course of clinical deterioration in these pa- tients.

References

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2. Victor M, Hayes R, Adams RD: Oculopharyngeal muscular dystrophy. A familial disease of late life characterized by dys- phagia and progressive ptosis of the eyelids. N Engl J Med 267:1267, 1962

3. Myrianthopoulos NC, Brown IA: A genetic study of progressive spinal muscular atrophy. Am J Hum Genet 6:387, 1954

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