GASTROENTEROLOGY. Official Publication of the American Gastroenterological Association

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1 GASTROENTEROLOGY Official Publication of the American Gastroenterological COPTBGBT 1969 Ts& WLL.um 4: WLKNS Co. VOLUME 56 January 1969 NUMBER 1 THE SWALLOWNG DSORDER N PATENTS WTH DABETC NEUROPATHY-GASTROENTEROPATHY PAUL MANDELSTAM M.D. CHARLES. SEGEL M.D. ARTHUR LEBER M.D. AND MAUREEN SEGEL Departments of Medicine and Radiology University of Kentucky College of Medicine Lexington Kentucky and Department of Medicine Johns Hopkins University School of Medicine Baltimore Maryland Manometric studies of the pharynx and esophagus in 8 patients with evidence of diabetic neuropathy-gastroenteropathy revealed in comparison with control patients marked diminution in the amplitude of pharyngeal contractions in the percentage of swallows followed by progressive peristalsis in the body of the esophagus in the amplitude of peristaltic contractions throughout the esophagus and in the effective lower esophageal intrasphincteric pressure. These observations serve further to delineate and quantitate the nature of the swallowing disorder which had previously been demonstrated cineradiographically in this same group of patients. Cineradiographic evidence of esophageal motor dysfunction has been previously reported by Mandelstam and Lieber l in 12 of 14 patients exhibiting other manifestations of diabetic neuropathy-gastroenteropathy. The salient features in the diabetic group as compared with findings in age- and sex-matched control subjects Received February Accepted June A portion of this work was presented at the annual meeting of the American Gastroenterological Association in Philadelphia Pennsylvania May Address requests for reprints to: Dr. Paul Mandelstam Department of Medicine University of Kentucky College of Medicine Lexington Kentucky This work was supported by the Research Committee and the Department of Medicine Research Fund both of the University of Kentucky. The authors wish to thank Ruth M. Jackson and Mary E. Smith for their excellent technical assistance. were absence or marked diminution in the primary peristaltic wave delay in esophageal emptying when the patient was recumbent and the presence of tertiary (spastic) contractions. No patient exhibited impairment of the cricopharyngeal sphincter. Only 3 of the patients had symptoms referable to the esophagus. Eleven of the 14 showed roentgenographic signs of gastric motor dysfunction; small intestinal examination was abnormal in 4. (Roentgenographic demonstration of food or fluid or both in the stomach after 8 hr or more of fasting sluggish peristalsis and delayed emptying were utilized as criteria of gastric dysfunction. Gastric emptying was considered delayed if most of the barium meal had not left the stomach within V2 hr. A small intestinal transit time of greater than 4 hr or presence of "deficiency pattern" or both were considered evidence of small intestinal dysfunction.)

2 2 MANDELSTAM ET AL. Vol. 56 No.1 Nine months to 3 years later the of the 14 original patients who were still alive were re-evaluated clinically and cineradiographically. To further delineate and quantitate the nature of the swallowing disorder manometric studies were carried out in the 8 who would consent. Material and Methods The diabetic subjects (2 women and 8 men) with evidence of neuropathy-gastroenteropathy ranged in age from 27 to 68; 7 were under age 40. The duration of known diabetes mellitus ranged from 3 to 34 years. Except for insulin none of the patients were taking medications known to influence gastrointestinal motility. Oral intake was discontinued 8 or more hr prior to the studies and the morning insulin dose was witheld. None of the patients exhibited hypoglycemic symptoms during the examinations. Blood urea nitrogen determinations revealed that none of them were azotemic. Urine specimens obtained from all patients within 30 min following completion of the manometric and cineradiographic studies in no instance revealed ketonuria or abnormal sediment. Cineradiographic studies of the esophagus were performed as previously described with the patient in the right anterior oblique-recumbent position with fluoroscopy and 16-mm cineradiography at a speed of 16 frames per sec. Observations were made of pharyngeal and esophageal caliber; rate of pharyngeal and esophageal emptying; presence or absence of tertiary (spastic) contractions; and presence diminution or absence of the primary peristaltic wave. Esophageal emptying was considered delayed if not completed within 20 sec after the initiation of swallowing. 2-4 For the investigation of hiatus hernia and gastroesophageal reflux the patients were examined in the prone oblique position. Manometric studies were performed as previously described 5 with the patients supine in 8 of the diabetic subjects and in a control group of 12 patients. The control group was matched for age and sex and included 3 women and 9 men with an age range of 22 to 65 (8 of the control subjects were under age 40). The controls had no evidence of diabetes mellitus esophageal symptoms or any neuromuscular disorder. Three water-filled open tipped polyvinyl catheters (internal diameter 1.4 mm) with tips positioned 5 cm apart were passed into the stomach and connected to Sanborn differential pressure transducers (267 B). Simultaneous pressures were recorded from 3 points by means of a multichannel direct writing recorder Sanborn model 350; respiratory excursions were monitored. The intermittent flush technique of recording was used the control group sphincteric resting pressures being in the range previously described 5 with this technique and lower than would have been obtained with the continuous infusion method. The pressure within the lower esophageal sphincter was recorded during stepwise withdrawal of the recording tip from the stomach into the esophagus. The esophagogastric junction was taken as the point of respiratory reversal. The recording tips were radio-opaque and were visualized fluoroscopically. By repeated withdrawal of the train of catheters from 4 to 9 technically satisfactory measurements of intrasphincteric pressure were obtained. The mean of the difference between intrasphincteric and intra gastric pressure was determined for each patient and was termed the mean effective intrasphincteric pressure. The duration of relaxation of the lower esophageal sphincter was also measured. Pressure recordings were obtained in the pharynx and at centimeter intervals throughout the body of the esophagus. At each level the amplitude of the peristaltic waves was measured in millimeters of mercury. The peak of the peristaltic wave minus the mean resting pressure was recorded as amplitude. The mean amplitude of contraction was then calculated for each level for each subject. All swallows were wet (i.e. after ingestion of a bolus of water). The computation of amplitude of contraction was based on only peristaltic contractions. The total number of swallows and the number which initiated peristalsis were recorded. The amplitude and duration of pharyngeal contractions were measured. The resting pressure within the upper esophageal (cricopharyngeal) sphincter and the duration of sphincter relaxation with swallowing were determined. For all determinations the mean and one standard deviation of all technically satisfactory observations were recorded. The raw data from which the means and standard deviations were obtained are available from the authors upon request. The diabetic patients were studied on two Jccasions 9 to 11 days apart. On the first visit interval histories were taken physical examinations carried out and cineradiographic examinations of the esophagus performed. On the sec-

3 January 1969 THE SWALLOWNG DSORDER 3 ond visit in which 8 of the diabetic subjects participated intraluminal esophageal manometric studies and cineradiography with the catheters in place were performed. n each patient the cineradiographic findings were substantially the same on both examinations. Clinical Cineradiographic and Manometric Case Summaries To facilitate comparison with the earlier findings in these patients the case numbers utilized in the previous study! have been retained. Case 1 History. This 25-year-old male has had known diabetes mellitus since age 16 and ~hen studied was taking 50 units of neutral protamine Hagedorn (NPH) insulin daily. There were no gastrointestinal tract symptoms at the time of study. Two years ago when he suffered fatty food intolerance and midepigastric postprandial pain unrelieved by food there was no roentgenographic evidence of peptic ulcer; no cineradiographic esophageal gastric or small intestinal motor dysfunction; and no abnormality on cholecystogram. He has had one episode of acidosis and frequent episodes of hypoglycemia but none of either within the last 2 years. There is no history of urinary tract infection nor of impotence. During the year prior to the present study he has felt well and worked regularly. was 5/65. Pupils reacted to light. Fundi were normal. Patellar reflexes were normal. One Achilles tendon reflex was normal the other absent. Position vibratory and pinprick sensations in the lower extremities were normal. Romberg sign was absent. Posterior tibial and dorsalis pedis pulsations were diminished. wave was diminished recumbent emptying delayed and esophageal caliber increased. Manometry. Not perforined. Case 2 History. This 27-year-old woman has had known diabetes since age 11 and at the time of study was taking 20 units of NPH insulin daily. There have been re- ---~ PHARYNX ~;' ::L~ ~==--= """".. '""''':: :1 o~ok-:: ' ~;~'.'~ '~'~~\~!~'!-~'~"~'~i ~'~! ~~J" ]i '" H9 50 ""'" ". ESOPHAGUS mm. 40t~ 20 o i o ii ' i! : '.u : ' ~! ~! iti i~1 ~'~ ~! " TME N SECONOS FG. 1. Manometric recording (patient 2) obtained with recordings tips in the pharynx (5 cm above the upper esophageal sphincter) in the cricopharyngeal sphincter and in the upper esophagus (5 cm below the sphincter). The pharyngeal contraction is decreased in amplitude and slightly increased in duration. The cricopharyngeus maintained a normal resting pressure and relaxed normally with deglutition. The upper esophageal contractions were of decreased amplitude. 'A

4 4 MANDELSTAM ET AL. Vol. 56 No.1 cent wide fluctuation in blood sugar frequent episodes of acidosis and hypoglycemia and frequent urinary tract infections. She has suffered for several years from postprandial abdominal distention and vomiting fatty food intolerance profound constipation and occasional rectal urgency. was 1/75. Pupils reacted poorly to light. There were retinal microaneurysms and hard exudates. Patellar and Achilles tendon reflexes were absent bilaterally. Romberg sign was absent. Pinprick position and vibratory sensations in the lower extremities were normal. Posterior tibial and dorsalis pedis pulsations were normal. wave was absent recumbent emptying delayed and esophageal caliber increased. Tertiary contractions were present. pharyngeal contractions was 15 mm Hg. The amplitude of peristaltic contractions throughout the esophagus was reduced (fig. 1). Progressive peristaltic contractions followed 52% of swallows. A moderate number of spastic contractions (i.e. segmental contractions in which the peak pressure was reached simultaneously at two points 5 to cm apart) were noted. The mean effective lower esophageal intrasphincteric pressure was 4 mm Hg above fundal pressure. Case 3 History. This 27-year-old male has had known diabetes since age 16 and when studied was taking 50 units of NPH insulin daily. He suffers impotence crippling orthostatic hypotension frequent episodes of nausea and vomiting diarrhea urinary retention and occasional rectal incontinence. He has had one episode of acidosis and frequent episodes of hypoglycemia. He has had repeated urinary tract infections. was 90/40 recumbent 62/0 sitting. Pupils reacted to light. Fundi were normal. Patellar reflexes were normal; Achilles tendon reflexes were absent. Position sense in the lower extremities was normal; vibratory and pinprick sensations were diminished. Romberg sign was equivocal. Posterior tibial and dorsalis pedis pulsations were normal. wave was absent recumbent esophageal emptying delayed and esophageal caliber dilated. pharyngeal contractions was 25 mm Hg. Progressive peristaltic contractions followed 43% of swallows. The amplitude of peristaltic contractions throughout the body of the esophagus was diminished moderately; occasional spastic contractions were noted. The mean effective lower esophageal intrasphincteric pressure was 2mmHg. Case 4 History. This 27-year-old male with known diabetes since age 19 was taking when studied 60 units of NPH insulin daily. There has been no history of acidosis hypoglycemia or urinary tract difficulty. He has had gradually diminishing vision over the past 2 years. He suffers weakness diminished libido impotence postprandial abdominal distress diarrhea and occasional rectal incontinence. was 5/70. Cataracts obscured both fundi. Pupillary reaction to light was diminished. Patellar reflexes were diminished and Achilles tendon reflexes were absent. Position vibratory and pinprick sensations in the lower extremities were normal. Romberg sign was absent. Posterior tibial and dorsalis pedis pulsations were normal. wave was diminished recumbent esophageal emptying delayed and esophageal caliber increased. pharyngeal contractions was 24 mm Hg. Progressive peristaltic contractions followed 94% of swallows. The amplitude of peristaltic contractions throughout the esophagus was moderately reduced. No spastic contractions were noted. The mean effective lower esophageal intrasphincteric pressure was 1 mm Hg.

5 January 1969 THE SWALLOWNG DSORDER 5 Case 5 History. This 35-year-old male has had known diabetes mellitus since age 6 and when studied was taking 60 units of NPH insulin daily. There have been no episodes of a~idosis but many episodes of hypoglycema. The only gastrointestinal tract symptoms have been occasional episodes of substernal burning following ingestion of spicy food. There has been no history of urinary tract infection. He is impotent. Cataract removal 4 years ago resulted in marked visual improvement but there has been marked diminution in vision during the past year. Six years ago he suffered at least one episode of acute myocardial infarction and during the year prior to study he has been taking digitalis and diuretics for congestive heart failure. was 5/75. The left eye was surgically absent (secondary to injury many years ago). The right eye was aphakic; a large fundal exudate was present. Patellar reflexes were normal; Achilles tendon reflexes were absent. Romberg sign was absent. Pinprick position and vibratory sensations in the lower extremities were normal. Posterior tibial and dorsalis pedis pulsations were normal. wave was absent. Recumbent emptying was delayed. Occasional tertiary contractions were noted. There was marked increase in esophageal caliber. pharyngeal contractions was 30 mm Hg. Progressive peristaltic contractions followed 37% of swallows. The amplitude of peristaltic contractions throughout the esophagus was substantially reduced. Frequent spastic contractions were noted (fig. 2) particularly in the upper half of the esophagus. The mean effective lower esophageal intrasphincteric pressure was 3mmHg. Case 6 History. This 36-year-dld male has had known diabetes since age 18 and when studied was taking 50 units of NPH insulin daily. He has had frequent episodes of ESOPHAGUS ;!:SOPHAGUS ; " "ESOPHAGUS 40 mm30~ mtt HQ 20 t- ~ o o io 3'0 4~ ~ 6~ 1~ 8~ 9~ :0 TME N SECONOS. FG. 2. Spastic esophageal contractions in response to deglutition (patient 5). Multiple repetitive contractons were noted. The recording tips were respectively 5 and 15 cm distal to the cricopharyngeal sphincter.

6 6 MANDELSTAM ET AL. Vol. 56 No.1 hypoglycemia but none of acidosis. Generalized weakness is a prominent symptom. Potency is diminished. There has been no history of urinary tract infections. Over the past 2 1/2 years he has had one stool per 72 hr and then only with laxation; preceding this period he suffered for 1 year from intermittent diarrhea with 6 to loose stools per 24 hr. was 160/0. The pupils were small and reacted minimally to light. Fundi were normal. Left patellar reflex was normal right was diminished; both Achilles tendon reflexes were absent. Position and vibratory sensations in the lower extremities were diminished on the left side and absent on the right. Pinprick sensation in the legs was diminished bilaterally but much more markedly on the right. Romberg sign was minimally positive. Posterior tibial and dorsalis pedis pulsations were normal. wave was diminished. Occasional tertiary contractions were noted. No other abnormalities were observed. Manometry. Not performed. Case 7 History. This 39-year-old male suffered two or more episodes of acute alcoholic pancreatitis years ago. Four years ago pancreatic calcifications were noted at the time acute onset diabetes mellitus was diagnosed. He has had two or three episodes of acidosis and many bouts of hypoglycemia. There have been no urinary tract infections. Over the past 4 years there has been marked depression profound anorexia and a 50-lb weight loss. For the past 2 years he has refused insulin and therefore when studied was being treated with 500 mg of chlorpropamide per day. He presently has one formed stool every 48 hr; in the past he has had intermittent episodes of loose stools. Cataract extractions were performed 4 months prior to study. was 150/80; height 5 ft. inches; weight 0 lb. The patient was very thin and appeared chronically ill. Both eyes were aphakic. There were hemorrhages exudates and microaneurysms in both fundi. Patellar and Achilles tendon reflexes were absent. Position sensation in the lower extremities was normal although vibratory sensation was markedly diminished. Romberg sign was absent. wave was absent recumbent esophageal emptying delayed and esophageal caliber increased. Occasional tertiary contractions were noted. pharyngeal contractions was 18 mm Hg. Progressive peristaltic contractions followed 16% of swallows. The amplitude of peristaltic contractions throughout the esophagus was markedly diminished. Spastic contractions were frequent. The mean effective lower esophageal intrasphincteric pressure was 2 mm Hg. Case 8 History. This 49-year-old woman has had known diabetes since age 35 and at the time of study was taking 30 units of NPH insulin daily. She has had many episodes of acidosis and hypoglycemia. Over the years she has had repeated urinary tract infections but none recently. She has noted numbness and diminished sensation in the feet for several years. She has had no gastrointestinal symptoms; when studied cineradiographicahy 2 years ago no esophageal motor abnormalities were noted. For several years she had been thyrotoxic secondary to a toxic nodule which had proved very resistant to radioactive iodine therapy; she has however been euthyroid for over 1 year prior to the presentstudy. was 160/90. Pupils reacted to light. Punctate hemorrhages and hard exudates were observed in both fundi. The thyroid was nodular and markedly enlarged. Patellar reflexes were normal Achilles tendon reflexes were absent. Position and vibratory sensations in the lower extremities were normal; pinprick sensation was diminished.

7 January 1969 THE SWALLOWNG DSORDER 7 Romberg sign was absent. Posterior tibial and dorsalis pedis pulsations were normal. wave was diminished recumbent esophageal emptying delayed and esophageal caliber increased. pharyngeal contractions was 21 mm Hg. Progressive peristaltic contractions followed 68% of swallows. The amplitude of peristaltic contractions throughout the esophagus was moderately diminished; occasional spastic contractions were noted. The mean effective lower esophageal intrasphincteric pressure was 2 mm Hg. Case History. This 60-year-old man has had known diabetes since age 16 and when studied was taking 55 units of NPH insulin per day. Over the years he has had two episodes of acidosis and many of hypoglycemia. There was one episode of urinary tract infection several years ago following prostatectomy. He has been impotent since age 32. Paresthesias of the lower extremities have been present for many years. Bilateral cataract extractions have been carried out. He has suffered repeated and severe staphylococcal carbuncles and abscesses. Over the past several years he has noted progressive dysphagia manifested by the sensation that food and fluids stick at the level of the suprasternal notch or pass through this region with great difficulty. t has often been necessary for him to apply pressure in that area after which swallowing proceeds asymptomatically. Cineradiographic examination of the esophagus 18 months prior to the present study revealed no abnormality in pharyngeal caliber or in the pharyngeal stage of deglutition. was 190/90. Both eyes were aphakic. Retinal examination revealed only moderate arteriolar narrowing. There was marked difficulty in the swallowing even of saliva and the patient at times gagged until he applied manual pressure to the suprasternal notch. Patellar reflexes were normal; Achilles tendon reflexes absent. Position vibratory and pinprick sensations in the lower extremities were markedly diminished. Romberg sign was positive. Posterior tibial and dorsalis pedis pulsations were normal. Cineradiography. Considerable pharyngeal dilation was noted and in the case of many swallows barium holdup was overcome only upon application of manual pressure to the suprasternal notch. Retention of barium in the valleculae and pyriforms was noted. n the esophagus no primary peristaltic waves were noted. Esophageal caliber was increased and esophageal emptying delayed. Occasional tertiary contractions were observed. Manometry. The mean amplitude and mean duration of pharyngeal contractions were 16 mm Hg and 0.92 sec respectively. The mean resting pressure and the mean duration of relaxation of the upper esophageal sphincter were 9 mm Hg and 0.58 sec respectively. Of 35 swallows none were followed by progressive peristaltic contractions in the body of the esophagus. Multiple spastic contractions were observed especially in the midportion of the esophagus. The mean effective lower esophageal intrasphincteric pressure was 1 mm Hg. This patient was the only one in this series in whom relaxation of the lower esophageal sphincter could not be detected. A mecholyl test was not performed because of electrocardiographic evidence of coronary artery disease. Case 12 History. This 69-year-old male has had a 3-year history of diabetes first detected in the course of investigation of lower extremity gangrene. He was taking at the time of study 500 mg of tolbutamide per day. There have been no episodes of acidosis or hypoglycemia no urinary tract infections and no gastrointestinal tract symptoms. He has had bilateral lower extremity amputations. For at least several months prior to amputation of the left leg because of gangrene of two toes there had been markedly diminished pin-

8 8 MANDELSTAM ET AL. Vol. 56 No.1 prick position and vibratory sensation below the knees. was 115/75. Pupils reacted to light. Bilateral cataracts were present. Arteriolar tortuosity constituted the only retinal abnormality. There were bilateral lower extremity amputations. wave was absent esophageal emptying delayed and esophageal caliber increased. Hiatus hernia and gastroesophageal reflux were present. pharyngeal contractions was 28 mm Hg. Progressive peristaltic contractions followed 55% of swallows. The amplitude mln.h '0 ".e. T ~.. " DABETCS T r --;-+-.. o~ ~ ~ FG. 3. Amplitude of pharyngeal contractions. The mean amplitude of pharyngeal contractions for each diabetic or control patient is indicated by a point. The mean amplitude for each population is indicated by a transverse line with one standard deviation also indicated TME. SECONDS T....-! :. DABETCS T -'-1- J. o~ ~ ~ FG. 4. Duration of pharyngeal contractions. The mean duration for each diabetic and control patient is indicated by a point. The mean for each population is shown by a transverse line and one standard deviation is also indicated.. Ht TOO ~- J. : DABETCS T.+ ".. o~ ~ ~ FG. 5. Upper esophageal sphincter resting pressure. Each point represents the mean resting pressure of the upper esophageal sphincter for a diabetic or control patient. The mean for each group is demonstrated by a transverse line and one standard deviation is indicated TME. SECONDS 0." T DABETCS T : -+- : J. o.l.- -L FG. 6. Upper esophageal sphincter duration of relaxation. The mean duration of relaxation for each diabetic or control patient is indicated by a point. The mean for each population group is shown by a transverse line and one standard deviation is indicated. of peristaltic contractions throughout the body of the esophagus was considerably diminished; occasional spastic contractions were noted. The mean effective lower esophageal intrasphincteric pressure was 3mm Hg. Results The amplitude of pharyngeal contractions in each of the 8 diabetic subjects was substantially less than the amplitude of the 12 control subjects. There was no overlap between groups (fig. 3). For the dia-

9 January 1969 THE SWALLOWNG DSORDER 9 betic group the mean was 22 ± 6 (1 sn) mm Hg and the range 15 to 30 mm Hg and for the control group the mean 40 ± 4 mm Hg and the range 36 to 47 mm Hg. The mean duration of pharyngeal contractions in the diabetics was 0.70 ± 0.14 sec (range 0.50 to 0.90 sec) compared to a ". 60 PERSTALSS AFTER 50 SWALLOWS FG. 7. Percentage of swallows followed by peristalsis. The height of each bar indicates the percentage of swallows initiating peristalsis in an individual diabetic subject and on the extreme right for the 12 control patients taken as a group. The number of swallows for each individual diabetic patient and for the entire control group is indicated by the number within the appropriate bar. mean of 0.55 ± 0.13 sec (range 0.30 to 0.70) in the controls (fig. 4); there was substantial overlap between groups. The mean resting pressure of the upper esophageal sphincter in the diabetic group was 14 mm Hg ± 3 with a range of 9 to 21; the control group mean resting pressure was 14 mm Hg ± 2 with a range of 11 to 17 (fig. 5). The mean duration of relaxation of the upper. esophageal sphincter in the diabetics was 0.64 ± 0. sec with a range of 0.48 to 0.77 sec; in the controls the mean was 0.80 ± 0.20 with a range of 0.55 to 1.3 sec (fig. 6). n both mean resting pressure and in duration of relaxation of the upper esophageal sphincter there was substantial overlap of the diabetic and the control groups. The percentage of swallows followed by peristalsis ranged from 0 to 94 % in the diabetic group; the average was 45% and in 6 of the 8 subjects was below 55%. n contrast in the 12 control patients the percentage of swallows followed by peristalsis averaged 89% and the range in the individual patients was from 80 to 0% (fig. 7). -.. EAN Of _-_.. EAN Of DABETCS ~50 E E \A E 40!) W W \A E A. 30 oj c z z 3 20 c E ~ Z O~ ~ r ~ ~ ~ 20 2~ em. ABOVE LOWER ESOPHAGEAL SPHNCTER FG. 8. Amplitude of peristaltic contraction. The mean amplitude of peristaltic contraction was calculated at each centimeter level of the esophagus for each diabetic and control patient. The mean of the diabetic and control patient populations for each level of the esophagus was then computed. The shaded areas represent the mean plus or minus one standard deviation for the diabetic and control populations respectively.

10 MANDELSTAM ET AL. Vol. 56 No UN 5.0 RESTNG PRESSURE. H ~:.:'wv:.:~~~c 4.0 PESSUE 3.0 z.. T ~ J. OABET CS T --:+- J. o~ ~ ~ FG. 9. Effective mean resting pressure in the lower esophageal sphincter. Each point represents the mean resting intrasphincteric pressure minus the gastric fundal pressure for a diabetic or a control patient. The population mean plus or minus one standard deviation is indicated. TME N SECONDS o~ ~ DABETCS FG.. Lower esophageal sphincter duration of relaxation. The mean duration of relaxation for each diabetic or control patient is indicated by a point. The mean for each population group is shown by a tran.sverse line and one standard deviation is indicated. The mean amplitude of peristaltic contractions was reduced throughout the body of the esophagus in 7 of the 8 diabetic subjects and in the remaining diabetic subject no peristaltic contractions followed any of 35 swallows (fig. 8). Spastic contractions were seen in 7 of the 8 diabetic subjects. They were observed in only 3 of the 12 control group patients; in none of them were they as frequent as in the 7 diabetic subjects. Of the 3 control group patients manifesting spastic contractions only 1 was under age 40. The mean effective lower esophageal intrasphincteric pressure in the diabetic group was 2 mm Hg ± 1 with a range of 1 to 4; in the control group the mean was 6 ± 1 with a range of 4 to 8 (fig. 9). There was minimal overlap between groups. The mean duration of relaxation of the lower esophageal sphincter in the diabetics was 5.6: sec ± 1.2 with a range of 4.0 to 7.5 sec; in the control group the mean m m. 40j Hg o mm.40 Hg o 40 mm. 30 Hg 20 o r f t rr - - j!.. :J. 1 j rd~ _. " L1 1-r l- '\-.-: t i- - l'" 1m 'fv i ~t L lj/t F"!' e27 t H'"..:11- ± + lt~. :'! l~ ~]~ ~ iii i i o TME N SECONDS FG. 11. Normal relaxation of the lower esophageal sphincter in response to deglutition (patient 12). The catheters are positioned respectively cm and 5 cm above the lower esophageal sphincter and in the sphincter itself.

11 Janoory 1969 THE SWALLOWNG DSORDER 11 was 5.9 sec ± 0.8 with a range of 5.0 to 7.0 sec (fig. ). The lower sphincter relaxed normally (fig. 11) in all diabetic subjects except patient in whom lower sphincter relaxation could not be detected. Discussion Manometric studies of the pharynx and esophagus in the patients with diabetic neuropathy-gastroenteropathy aided very considerably in the further delineation and quantitation of the nature and severity of the abnormalities demonstrated in these same patients by cineradiography both earlier and in the present investigation. n comparison with an age- and sexmatched control patient group the diabetic subjects exhibited marked diminution in the amplitude of peristaltic contractions in the pharynx and throughout the body of the esophagus a markedly decreased percentage of swallows followed by peristalsis a high incidence of tertiary (spastic) contractions and a much diminished resting pressure in the lower esophageal sphincter. n contrast there was substantial overlap between diabetic and control patient groups in mean duration of pharyngeal contractions in mean resting pressure and duration of relaxation of the upper esophageal sphincter and in duration of relaxation of the lower esophageal sphincter. Several aspects of the present findings are noteworthy. n the earlier study 1 of the 14 diabetic subjects patients 1 and 8 were the only ones in whom cineradiographic examinations of the esophagus were entirely normal. Both of these subjects when restudied cineradiographically 2 years later manifested diminution in the primary peristaltic wave delayed recumbent emptying and increase in esophageal caliber. Patient 1 had had gastrointestinal tract symptoms at the time of the earlier study but was asymptomatic when restudied; patient 8 has had no gastrointestinal difficulties. Patient when studied 18 months previously revealed no cine radiographic evidence of pharyngeal or upper esophageal sphincter difficulty although his dysphagia had been almost as severe as at the time of the restudy. The repeat cineradiographic studies did however reveal considerable pharyngeal dilation and substantial abnormality in the pharyngeal stage of deglutition. This patient was the only diabetic subject to exhibit cineradiographic evidence of pharyngeal abnormality. n contrast manometry revealed a marked diminution in the amplitude of pharyngeal contractions in all of the diabetic subjects. lntraluminal manometry is a more sensi ;ive technique for measurement of the amplitude and duration and coordination of pharyngeal contractions. t is thus a valuable complementary technique to cineradiography which gives information on dilation or constriction of the pharyngeal structures flow characteristics and adequacy of pharyngeal emptying with deglutition.. n this study of patients with diabetic neuropathy-gastroenteropathy as in Soergel and co-workers' investigation of the very elderly2 intraluminal manometry revealed a higher incidence of primary peristaltic contractions in the body of the esophagus than did cineradiography alone. The longer period of observation with intraluminal manometry and perhaps the greater sensitivity of the method enable one to assess more accurately the relative frequency of peristaltic and nonperistaltic contractions. Of the 8 diabetic subjects studied both manometrically and cineradiographically manometry demonstrated primary peristaltic contractions in 7 of the 8 and cineradiography in only 2. Similarly spastic contractions were demonstrated by cineradiography in only 4 of the 8 while by manometry they were demonstrated in 7. t should be noted that the diabetic patients selected for this study were those with evidence of neuropathy-gastroenteropathy it seeming most improbable that the esophagus would remain invariably maffected under circumstances in which gastric and small intestinal motor dysfunction are not uncommon. We have not stud~ ied esophageal motor function in diabetic subjects in whom signs and symptoms of diabetic neuropathy-gastroenteropathy are

12 12 MANDELSTAM ET AL. Vol. 56 No.1 absent and therefore have not ruled out the possibility that the manifestations of esophageal motor dysfunction which we have noted are a feature of the diabetic state per se. These studies in patients with diabetic neuropathy-gastroenteropathy revealed both similarities and differences when compared with the findings of Soergel and co-workers 2 3 in subjects aged 90 or above. n both groups there is a high incidence of tertiary contractions and a marked diminution in the percentage of swallows which result in progressive peristaltic contractions in the body of the esophagus. n the diabetic group however the amplitude of progressive contractions throughout the esophagus is markedly diminished; in the nonagenarians those swallows which result in peristalsis yield contractions of normal amplitude. The mean resting pressure of the lower esophageal sphincter is markedly reduced in the diabetic subjects; it is substantially normal in the nonagenarians. There are similiarities and differences too between the findings in the subjects with diabetic neuropathy-gastroenteropathy and in the patients with myotonia dystrophica studied by Siegel et al. 5 n both groups the amplitude of peristaltic contractions in the pharynx is markedly reduced. n the myotonia group however the duration of pharyngeal contractions is markedly prolonged while in the diabetics prolongation is minimal. The resting pressure in the upper esophageal sphincter is normal in the diabetics; it is diminished in the group with myotonia. The duration of relaxation of the upper esophageal sphincter is increased in the myotonia group whereas it is somewhat diminished in the diabetic group. n general the involvement of pharynx and cricopharyngeus is more prominent in the patients with myotonia dystrophica. n both groups the percentage of swallows followed by progressive peristaltic contractions in the body of the esophagus is diminished and in both the amplitude of peristaltic contractions in the esophagus is markedly reduced. The effective mean resting pressure in the lower esophageal sphincter is markedly reduced in the diabetics whereas it is for the most part normal in the myotonia group. From a clinical standpoint too the myotonia and the diabetic groups can be contrasted: incompetence of the upper esophageal sphincter with regurgitation of liquids into the nasopharynx is frequent in the myotonia group and was found in no patients of the diabetic neuropathy-gastroenteropathy group. 1 These findings parallel the involvement of the upper esophageal sphincter as evidenced manometrically in contrast to the normal findings in the patients with diabetic neuropathy-gastroenteropathy. The gagging observed in diabetic patient the only diabetic subject so afflicted was on the basis of impaired pharyngeal emptying rather than due to esophago-pharyngeal reflux. REFERENCES 1. Mandelstam P. and A. Lieber Esophageal dysfunction in diabetic neuropathy-gastroenteropathy-clinical and roentgenological manifestations. J. A. M. A. 201: Soergel K. H. F. F. Zboralske and J. R. Amberg Presbyesophagus: esophageal motility in nonagenarians. J. Clin. nvest. 43: Zboralske F. F. J. R. Amberg and K. H. Soergel Presbyesophagus: cineradiographic manifestations. Radiology 82: Lorber S. H. and C. J. D. Zarafonetis Esophageal transport studies in scleroderma. Amer. J. Med. Sci. 245: Siegel C.. T. R. Hendrix and J. C. Harvey The swallowing disorder in myotonia dystrophica. Gastroenterology 50: