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Gastroduodenal motility in a case of dystrophia myotonica
GASTROENTEROLOGY
CASE
1981;81:145-9
REPORTS
Gastroduodenal Motility in a Case of Dystrophia Myotonica T. D. LEWIS and E. E. DANIEL Departments Canada
of Medicine
and Neurosciences,
A 53-year-old man with dystrophia myotonica developed symptoms of a chronic intestinal motility disorder. lncoordinate small bowel contractions as well as dilated segments were observed on x-ray examination. Gastroduodenal manometry in the fasted state showed contractions of reduced amplitude. A migrating motor complex occurred in the basal state. Pentagastrin and edrophonium injections increased motility; a liquid meal was followed by a normal motor response. The maximum gastric contraction rate (after pentagastrin injection) was 3.8/min. The maximum duodenal contraction rate observed at each duodenal recording site varied between 11.0 and 18.5/min. The lowest rate at each recording site was 11.1, 21.5, 21.0, and 12,2/min, while the fastest rate was 17.6, 16.6, 18.5, and 17.6/min. These maximum rates occurred independently of the rates at adjacent sites and of the drug infusions. The gastroduodenal motor abnormality in this patient thus predominantly affects smooth muscle, with the intrinsic neurons able to release acetylcholine and the muscle capable of responding to it. The results may indicate that electrical control activity in the duodenum intermittently oscillates more rapidly than normal, and when this occurs, phase-locking is absent. We conclude that in dystrophia myotonica there may be a defect in the cell membrane, which can cause more frequent electrical oscillations of the cell; alternatively, there may be a defect in cell-to-cell coupling. Dystrophia myotonica is a chronic familial condition characterized by myotonia and wasting of skeletal muscle; its onset is in adult life. Gastrointestinal smooth muscle may also be involved: esophagus (l7) (decrease in or loss of esophageal peristalsis); stomach (8,9) (impaired gastric emptying); small Received February 18,198O. Accepted January 12, 1981. Address requests for reprints to: Terence D. Lewis, M.D., Section of Gastroenterology, Loma Linda University, Loma Linda, California 92350. The authors thank Shirley Smith for secretarial assistance. 0 1981 by the American Gastroenterological Association 0016-5085/81/070145-05$02.50
McMaster
University,
Hamilton,
Ontario,
bowel (10-13) (with small bowel dilatation, prolonged transit time, and steatorrhea; pseudoobstruction syndrome [14,15]); colon (7,16) (constipation or diarrhea and dilated atonic colon); and anal spincter (2,17) (myotonic contraction of both the internal and external anal sphincters). We present here the gastric and duodenal manometric findings in a patient with dystrophia myotonica with some of the symptoms and features of a secondary chronic intestinal pseudoobstruction syndrome.
Case Report LB., a Syr-old
male, developed symptoms of dys-
trophia myotonica in the mid-1960% confirmed by eiectromyogram in 1973. He had a brother with the same disease. Gastrointestinal symptoms developed in 1976 and necessitated several admissions to hospital. During one episode, he had a distended abdomen with decreased bowel sounds and dilated small bowel on x-ray, although
no air-fluid levels were seen (fecal impaction had been excluded). His symptoms gradually subsided without therapy, and a chronic motility disorder was considered likely. He did not give a history of chronic laxative abuse. These symptoms repeatedly returned, the major symptom being recurrent, persistent vomiting. He was referred to McMaster University Medical Center in February, 1978, for further investigation, as his vomiting had returned. On admission he was bedfast, with marked muscle wasting (most prominent in his hands and neck) and weakness of all muscle groups, with hyporeflexia and bilateral ptosis; sensation was normal, and he had frontal baldness. Abdominal examination was within normal limits, with normal bowel sounds. Investigation An upper gastrointestinal x-ray series was performed with small bowel follow-through. The esophagus showed deficient primary peristalsis with numerous tertiary contractions; the stomach showed little peristalsis, and the distal antrum was narrowed, although transient relaxation was seen with intravenous buscopan (a shortacting anticholinergic drug). Gastric emptying of barium
146
LEWIS AND DANIEL
GASTROENTEROLOGY
Vol. 81,No. 1
tric antral pressure while the remaining side holes recorded duodenal motility. Pressures were recorded with the patient supine after an overnight fast of 12 h.
Results Basal Activity
I
24
I
37
I
49
I
62
I
75
TIME (min.) Figure1.Gastric emptying study: while t,,, is normal, the slope of the curve is abnormal as it is not the usual straight line after the initial 10 min.
was not delayed. The small bowel showed intermittent transient dilatation involving duodenum, jejunum, and ileum: incoordinate peristalsis was also seen. The small bowel transit time of the head of the barium column was 2.5 h (normal for our methods). Gastric emptying of a radioactively labeled egg sandwich (18) occurred with a normal half-emptying time (t,,,)
of 60 min, but with an unusual time sequence (Figure 1) during an asymptomatic period. Barium enema disclosed a shortened left colon and a loss of haustration (resembling a “burnt-out” ulcerative colitis). Sigmoidoscopy and rectal biopsy specimens were within normal limits. Esophageal motility study confirmed the radiology appearance with absent peristalsis, being replaced by feeble simultaneous contractions of low amplitude.
During the basal period, intermittent contractile activity was seen at all recording sites. Twenty-three minutes from the start of recording, contractions at the maximal rate were seen at the middle recording hole, and this maximal activity propagated distally. No preceding gastric phase was seen. This contractile activity showed all of the features of a migrating motor complex at 3 of the duodenal recording sites. The duration of the complex was 5 min 20 s, the velocity of propagation was 0.36 cm/s. After this complex, duodenal motor activity was absent for 13 min 12 s. The maximum amplitude of duodenal contractions was 29 cm H,O (normal for our laboratory is 68 cm H,O f 18 SD). This motor activity was no different than that seen in normals in our laboratory (19), apart from the maximal rate of contraction seen, which is discussed in detail below. Response to Pentagastrin Pentagastrin, infused 74 min after the start of recording, increased the rate of contractile activity in the stomach and duodenum, but not the amplitude (Table 1). Five minutes after the injection of pentagastrin, gastric and duodenal contractions began occurring at the maximal rate; this activity propagated aborally, with all the features of a migrating
Table
1.
Motor Response
to Pentagastrin
Before pentagastrin
After pentagastrin (min)
(min)
Gastroduodenal
5
Manometry
The tube assembly consisted of five polyvinyl tubes (ID, 0.5 mm) bonded together with tetrahydrofuran; side holes were 5, 12.5, 20, and 27.5 cm above the most distal side hole. The tubes were continuously perfused with 0.9% saline at a pressure of 20 lb./in.’ by an Arndorfer constant infusion pump (Arndorfer Instruments, Greendale, Wis.), pressures were recorded by Statham P23 series transducers (Statham Instruments, Hato Ray, Puerto Rico), and the write-out was on a Beckman R611 Dynograph (Beckman Instruments, Fullerton, Calif.). This recording system showed low compliance with sudden occlusion producing a rise of 600 cm H,O/s. The tube was passed by mouth and positioned fluoroscopically with the tip in the third part of the duodenum; the tube was fixed at the patient’s mouth. The proximal side hole recorded gas-
4
3
Number of contractions” Gb 0 0 0 DIG Dz D, D4
Mean Gb D,” D, D, D,
2
112
0 0 0 2 0 12 0 0 0 4 0 13 0 0 210 0 3 1 0 0 0 9 1 1 0 0 0 3 13 Mean=3flSD Mean = 32 f amplitude of contractions (cm H,O) 0 0 0 0 0 0 22 0 10 11 0 0 0 10 0 10 13 0 0 15 19 0 7 13 0 0 0 18 6 8 0 0 0 9 18 Mean = 10 f 2 cm Hz0 SD Mean = 11 f
3
4
4 0 7 10 8 8 6 16 8 6 13 SD 40 8 10 10 12 3 cm
5
2 5 10 10
0 29 5 0 6 8 12 15 10 16 H,O SD
0 Only counting contractions >5 cm HZO. b G = gastric contractions.= D,_, = duodenal contractions from proximal to distal.
July 1981
ABNORMAL MOTILITY IN MYOTONIC DYSTROPHY
motor complex (Figure 2). This complex occurred 57 min after the first complex was recorded (this subject’s usual period between complexes was not determined). The duration of maximal activity in the duodenum was 4 min 16 s (normal: 6 min 21 s f 2 min 19 s SD) (19), followed by a 9-min 13-s period of inhibition of motor activity (normal: 9 min 50 s + 5 min 11 s SD) (19). The time taken for the complex to travel 1 cm was 12.5 s (normal 9.9 + 6.4 s SD) (19).
Table
Response to Edrophonium Edrophonium HCl, given 23 min after the start of pentagastrin injection, was followed by an increase in the number and amplitude of duodenal contractions (see Table 2); edrophonium did not affect gastric antral contractions. Response to a Liquid Meal Sustacal of gastric antral the number of same response trols.
was followed by the disappearance contractions and a slight increase in duodenal contractions. This is the as observed in several normal con-
Maximal Rate of Contractions The contraction rate was counted when maximum contractile activity occurred, in order to estimate the rate of electrical control activity. This maximal activity was considered present when there was a persistent regular pattern of contraction, without dropped contractions. This occurred sometimes
2.
Motor
Response to Edrophonium
Before edrophonium (min) __--
5
4
147
3
Number of contractions’ G” 1 1 0
After edrophonium (min)
.I_-
2
112
3
4
5
D,C
0
0
1
0 0
1 1
0 1
0 5
0 8
1 3
1 5
D,
0 0 0
0 0 0
1 0 0
1 2 0
1 0 1
3 4 3
1 9 7
0 16 0
1 4 5
1 7 3
16 17 16 14 15
31 19 21 9 30
D, D,
Mean=ZflSD Mean = 24 + 19 SD Mean amplitude of contractions0 (cm H,O) G” D,’ D, D:, D,
111 0 Q 0 0
109 0 0 0 0
0 10 7 0 0
0 0 15 8 0
96 5 7 0 9
Mean = 10 rt 4 cm Hz0 SD
0 5 17 15 42
0 20 13 9 17
0 25 0 12 0
Mean = 18 f 6 cm H,O SD
” Including only contractions >5 cm HZO. b G = gastric contractions.” D1_4= duodenal contractions from proximal to distal.
during intermittent motor activity and always during a migrating motor complex. The maximum rate of contraction was then calculated as the inverse of the duration from the onset of one contraction to the onset of a subsequent contraction (the number of contractions counted ranging from 5 to 38 in the duodenum) and expressed as the number of contractions per minute. Similar values were calculated when the contraction rate was measured from the point of maximal amplitude of one contraction to that of a subsequent contraction. The duodenal contraction rates during maximal activity were as high as 18.5/min and as low as ll.O/min. The results at
Figure 2. Response of the stomach and duodenum to injection of pentagastrin, 0.3 /&kg i.v. The orrows indicate the injection of pentagastrin. R = respiration, G = gastric, D,-D, = duodenal recording sites from orad to aborad. The black dots mark artifacts in the record. A migrating motor complex commences 5 min after the injection of pentagastrin.
148
LEWIS AND DANIEL
GASTROENTEROLOGY
Table 3. Maximum Contraction Rate” Occurring at Each Recording Site
Basal Gastric Duodenal 1’
17.8(5)b
Duodenal 2
11.5(9)
Duodenal 3
17.1(5), 17.5(7), 16.7(5)
Duodenal 4
11.2(38)
Postpentagastrin 3.8(3)b 15.3(11), 11.1(18) 18.6(8), 11.8(10), 14.4(6) 16.7(12), 11.7(17)
17.4(11), 11.4(23)
Postedrophonium
12.2(6) -
lLO(10)
-
Postsustacal
16.2(7)b
12.9(12), 11.7(7), 15.7(11), 16.2(5), 14.2(y), 14.4(6), 13.7(9), 18:5(8) 17.8(12)
a Contractions per minute. b The numbers in parentheses indicate the number of contractions that were counted to calculate the contraction rate. c Duodenal l-4 signify the position of the recording site within the duodenum from orad to aborad.
each site seen did drugs or odenum, complex.
are shown in Table 3. The contraction rates not appear to be related to the effects of food, to the site of recording within the duor to the presence of a migrating motor
Discussion In dystrophia myotonica, abnormal esophageal (l-7) gastric (7-g), small bowel (X1-13), and coionic (7,16) motor dysfunctions have been described. Our studies showed abnormal motor function of the esophagus, stomach, duodenum, and colon. The involvement of cholinergic nerves in the production of disordered gastric and duodenal function was investigated by studying the effects of a meal, pentagastrin, and edrophonium. The motor activity intiated by a meal involves vagal activity (20). Edrophonium acts by preserving acetylcholine released by nerves, and pentagastrin by releasing acetylcholine from nerves in vivo (21,22). The meal produced the usual pattern of change in motor activity which we observe. Edrophonium increased duodenal but not antral motility as in our normal subjects (19). Pentagastrin increased antral and duodenal motility as in normal subjects (21). Soon after its injection, a migrating motor complex was seen; this was unlikely to be spontaneous as pentagastrin usually inhibits such complexes (23-25) but possibly triggered by the cessation of pentagastrin effects as in dogs (24). (Pentagastrin would be expected to have a shorter plasma half-life than gastrin-17, which is 6
Vol. 81, No. 1
min [26].) These data, as Well as morphologic studies of other such patients (27), indicate that cholinergic nerves may be structur$ly and functionally normal (within the limits of the procedures). (Function of inhibitory nerves was not. examined in this study.) The major abnormality of motor function we observed was an increased (up to- 18.5/min) and variable (down to Wmin) maximal rate of contraction in the duodenum. As the maximal rate of duodenal contraction is normally controlled by the maximum rate of electrical control activity (ECA) (28) this implies an increase in ECA frequency. If our duodenal probes sometimes did not record a contraction because in the dilated duodenum it failed to occlude the lumen, this would suggest that the ECA rate is even faster than the ma&mum contraction rate recorded. Our records do not suggest that missed contractions were occurring. The simplest hypothetical explanation for increased ECA frequency is a partial depolarization of duodenal smooth muscle cells resulting from damage to smooth muscle (increased leakiness to Na’ and/or Ca’+), with decreased activity of membrane electrogenic ion pump (similar changes to that seen in skeletal muscle [29]). It is conceivable that each probe recording duodenal contraction may in this case have been picking up activity initiated from a region large enough to include more than that occupied by a single electrical control wave. This is possible in this case as his ECA appeared to be unphase-locked, as judged by the varying contraction frequencies at adjacent sites. As a result of this, a higher frequency of lower amplitude contractions might be recorded; however, the regularity of contraction (during periods when contractions occurred at the maximum rate) would make this unlikely. The evaluation of these hypotheses will require direct electrophysiologic study of ECA and of membrane potentials in smooth muscle cells from such a patient. Increased ECA frequency could account for the absence of phase-locking (varied contraction frequencies in the duodenum at a given time) in the duodenum. This would occur if the frequencies of some pacemakers exceeded the ability of many regions to follow (28). Lack of continuous phase-locking of the duodenum could account for the variable gastric emptying shown by this patient as duodenal contents may not be rapidly cleared during periods of unlocking (peristaltic spread of contractions would be absent). Although we only,recorded from one antral site, this phenomenon could also be present intermittently within the stomach and could account for the vomiting. An alternate explanation for the failure of phase-locking in the duodenum is damage to cell-to-cell coupling (which may explain in part the loss of esophageal peristalsis [30]). This pos-
July1981
sibility could be evaluated by functional and structural studies of duodenal muscle. In conclusion, disordered gastrointestinal motility was widespread in a patient with dystrophia myotonica. The most striking changes were increased frequency and absence of phase-locking of the phasic contractions of the duodenum. These might result from damage to and depolarization of smooth muscle cells and could contribute to or be responsible for the vomiting that occurred.
ABNORMAL MOTILITY IN MYOTONIC DYSTROPHY
17.
18.
19.
20.
References 1. Kelley ML Jr. Dysphagia and motor failure of the esophagus in myotonia dystrophica. Neurology 1964;14:955-60. 2. Harvey JC, Sherbourne DH, Siegel CI. Smooth muscle involvement in myotonic dystrophy. Am J Med 1965;39:81-90. 3. Pierce JW, Creamer B, MacDermot V. Pharynx and oesophagus in dystrophia myotonica. Gut 1965:6:392-5. 4. Schuman BM, Rinaldo JA Jr, Darnley JD. Visceral changes in myotonic dystrophy. Ann Intern Med 1965;63:793-9. 5. Siegel CI, Hendrix TR, Harvey JC. The swallowing disorder in myotonia dystrophica. Gastroenterology 1966;50:541-50. 6. Garrett JM, et al. Esophageal and pulmonary disturbances in myotonia dystrophica. Arch Intern Med 1969;123:26-32. 7. Goldberg HI, Sheft DJ. Esophageal and colon changes in myotonia dystrophica. Gastroenterology 1972;63:134-9. 8. Kuiper DH. Gastric bezoar in a patient with myotonic dystrophy. Am J Dig Dis 1971;16:529-34. 9. Waring JJ, Ravin A, Walker CE Jr. Studies in dystrophia myotonica. Arch Intern Med 1940;65:763-99. 10.Kaufman KK, Heckert EW. Dystrophia myotonica with associated sprue-like symptoms. Am J Med 1954;16:614-6. 11.Welsh JD, Gunter RH, Bynum TE. Myotonic muscular dystrophy. Arch Intern Med 1964;114:669-79. 12. Chiu VSW, Englert E. Gastrointestinal disturbances in myotonia dystrophica (abstr). Gastroenterology 1962;42:745-6. 13. Lups S. Myotonic dystrophy with steatorrhea. Acta Med Stand 1941;106:557-78. 14. Moss AA, Goldberg HI, :Brotman M. Idiopathic intestinal pseudoobstruction. Am f Roentgen01 1972;115:312-7. 15. Faulk DL, Anuras S, Christensen J. Chronic intestinal pseudoobstruction. Gastroenterology 1978;74:922-31. 16. Kohn NN, Aires JS, Rodman T. Unusual manifestations due to
21. 22.
23
24
25
26
27. 28.
29. 30.
149
involvement of involuntary muscle in dystrophia myotonica. N Engl J Med 1964;271:1179-83, Schuster MM, Tow DE, Sherbourne DH. Anal sphincter abnormalities characteristic of myotonic dystrophy. Gastroenterology 1965;49:641-8. Coates G, Gilday DL, Cradduck TD, et al. Measurement of the rate of stomach emptying using Indium-113m and a IO-crystal rectilinear scanner. Can Med Assoc J 1973;108:180-3. Lewis TD, Collins SM, Fox JE, et al. Initiation of duodenal acid-induced motor complexes. Gastroenterology 1979; 77:1217-24. Diamant NE, Hall K, Mui H, et al. Vagal control of the feeding motor pattern in the lower esophageal sphincter, stomach and upper small intestine of the dog. In: Christensen J, ed. Gastrointestinal motility. New York: Raven Press, 1980:36570. Smith AN, Hogg D. Effect of gastrin II on the motility of the gastrointestinal tract. Lancet 1966;1:403-4. Cook MA, Kowalewski K, Daniel EE. Electrical and mechanical activity recorded from the isolated perfused canine stomach: the effects of some GI polypeptides. In: Daniel E, ed. Proceedings of the Fourth International Symposium of Gastrointestinal Motility. Vancouver: Mitchell Press, 1974: 233-42. Weisbrodt NW, Copeland EM, Kearley RW. et al. Effects of pentagastrin on electrical activity of small intestine of the dog. Am J Physiol 1974;277:425-9. Marik F, Code CF. Control of the interdigestive myoelectric activity in dogs by the vagus nerves and pentagastrin. Gastroenterology 1975;69:387-95. Wingate DL, Pearce EA, Hutton M, et al. Quantitative comparison of the effects of cholecystokinin, secretin, and pentagastrin on gastrointestinal myoelectric activity in the conscious fasted dog. Gut 1978;19:593-601. Walsh JH, Isenberg JI, Ansfield J, Maxwell V. Clearance and acid-stimulating action of human GIV and little gastrins in duodenal ulcer patients. J Clin Invest 1976;57:1125-31. Pruzanski W, Huvos AG. Smooth muscle involvement in primary muscle disease. Arch Path01 1967;83:229-33. Daniel EE, Sarna S. The generation and conduction of activity in smooth muscle. Ann Rev Pharmacol Toxic01 1978;18:14566. Harper PS. Myotonic dystrophy. Philadelphia: WB Saunders, 1979. Sarna SK, Daniel EE, Waterfall WE. Myogenic and neural control systems for esophageal motility. Gastroenterology 1977;73:1345-52.
CASE
1981;81:145-9
REPORTS
Gastroduodenal Motility in a Case of Dystrophia Myotonica T. D. LEWIS and E. E. DANIEL Departments Canada
of Medicine
and Neurosciences,
A 53-year-old man with dystrophia myotonica developed symptoms of a chronic intestinal motility disorder. lncoordinate small bowel contractions as well as dilated segments were observed on x-ray examination. Gastroduodenal manometry in the fasted state showed contractions of reduced amplitude. A migrating motor complex occurred in the basal state. Pentagastrin and edrophonium injections increased motility; a liquid meal was followed by a normal motor response. The maximum gastric contraction rate (after pentagastrin injection) was 3.8/min. The maximum duodenal contraction rate observed at each duodenal recording site varied between 11.0 and 18.5/min. The lowest rate at each recording site was 11.1, 21.5, 21.0, and 12,2/min, while the fastest rate was 17.6, 16.6, 18.5, and 17.6/min. These maximum rates occurred independently of the rates at adjacent sites and of the drug infusions. The gastroduodenal motor abnormality in this patient thus predominantly affects smooth muscle, with the intrinsic neurons able to release acetylcholine and the muscle capable of responding to it. The results may indicate that electrical control activity in the duodenum intermittently oscillates more rapidly than normal, and when this occurs, phase-locking is absent. We conclude that in dystrophia myotonica there may be a defect in the cell membrane, which can cause more frequent electrical oscillations of the cell; alternatively, there may be a defect in cell-to-cell coupling. Dystrophia myotonica is a chronic familial condition characterized by myotonia and wasting of skeletal muscle; its onset is in adult life. Gastrointestinal smooth muscle may also be involved: esophagus (l7) (decrease in or loss of esophageal peristalsis); stomach (8,9) (impaired gastric emptying); small Received February 18,198O. Accepted January 12, 1981. Address requests for reprints to: Terence D. Lewis, M.D., Section of Gastroenterology, Loma Linda University, Loma Linda, California 92350. The authors thank Shirley Smith for secretarial assistance. 0 1981 by the American Gastroenterological Association 0016-5085/81/070145-05$02.50
McMaster
University,
Hamilton,
Ontario,
bowel (10-13) (with small bowel dilatation, prolonged transit time, and steatorrhea; pseudoobstruction syndrome [14,15]); colon (7,16) (constipation or diarrhea and dilated atonic colon); and anal spincter (2,17) (myotonic contraction of both the internal and external anal sphincters). We present here the gastric and duodenal manometric findings in a patient with dystrophia myotonica with some of the symptoms and features of a secondary chronic intestinal pseudoobstruction syndrome.
Case Report LB., a Syr-old
male, developed symptoms of dys-
trophia myotonica in the mid-1960% confirmed by eiectromyogram in 1973. He had a brother with the same disease. Gastrointestinal symptoms developed in 1976 and necessitated several admissions to hospital. During one episode, he had a distended abdomen with decreased bowel sounds and dilated small bowel on x-ray, although
no air-fluid levels were seen (fecal impaction had been excluded). His symptoms gradually subsided without therapy, and a chronic motility disorder was considered likely. He did not give a history of chronic laxative abuse. These symptoms repeatedly returned, the major symptom being recurrent, persistent vomiting. He was referred to McMaster University Medical Center in February, 1978, for further investigation, as his vomiting had returned. On admission he was bedfast, with marked muscle wasting (most prominent in his hands and neck) and weakness of all muscle groups, with hyporeflexia and bilateral ptosis; sensation was normal, and he had frontal baldness. Abdominal examination was within normal limits, with normal bowel sounds. Investigation An upper gastrointestinal x-ray series was performed with small bowel follow-through. The esophagus showed deficient primary peristalsis with numerous tertiary contractions; the stomach showed little peristalsis, and the distal antrum was narrowed, although transient relaxation was seen with intravenous buscopan (a shortacting anticholinergic drug). Gastric emptying of barium
146
LEWIS AND DANIEL
GASTROENTEROLOGY
Vol. 81,No. 1
tric antral pressure while the remaining side holes recorded duodenal motility. Pressures were recorded with the patient supine after an overnight fast of 12 h.
Results Basal Activity
I
24
I
37
I
49
I
62
I
75
TIME (min.) Figure1.Gastric emptying study: while t,,, is normal, the slope of the curve is abnormal as it is not the usual straight line after the initial 10 min.
was not delayed. The small bowel showed intermittent transient dilatation involving duodenum, jejunum, and ileum: incoordinate peristalsis was also seen. The small bowel transit time of the head of the barium column was 2.5 h (normal for our methods). Gastric emptying of a radioactively labeled egg sandwich (18) occurred with a normal half-emptying time (t,,,)
of 60 min, but with an unusual time sequence (Figure 1) during an asymptomatic period. Barium enema disclosed a shortened left colon and a loss of haustration (resembling a “burnt-out” ulcerative colitis). Sigmoidoscopy and rectal biopsy specimens were within normal limits. Esophageal motility study confirmed the radiology appearance with absent peristalsis, being replaced by feeble simultaneous contractions of low amplitude.
During the basal period, intermittent contractile activity was seen at all recording sites. Twenty-three minutes from the start of recording, contractions at the maximal rate were seen at the middle recording hole, and this maximal activity propagated distally. No preceding gastric phase was seen. This contractile activity showed all of the features of a migrating motor complex at 3 of the duodenal recording sites. The duration of the complex was 5 min 20 s, the velocity of propagation was 0.36 cm/s. After this complex, duodenal motor activity was absent for 13 min 12 s. The maximum amplitude of duodenal contractions was 29 cm H,O (normal for our laboratory is 68 cm H,O f 18 SD). This motor activity was no different than that seen in normals in our laboratory (19), apart from the maximal rate of contraction seen, which is discussed in detail below. Response to Pentagastrin Pentagastrin, infused 74 min after the start of recording, increased the rate of contractile activity in the stomach and duodenum, but not the amplitude (Table 1). Five minutes after the injection of pentagastrin, gastric and duodenal contractions began occurring at the maximal rate; this activity propagated aborally, with all the features of a migrating
Table
1.
Motor Response
to Pentagastrin
Before pentagastrin
After pentagastrin (min)
(min)
Gastroduodenal
5
Manometry
The tube assembly consisted of five polyvinyl tubes (ID, 0.5 mm) bonded together with tetrahydrofuran; side holes were 5, 12.5, 20, and 27.5 cm above the most distal side hole. The tubes were continuously perfused with 0.9% saline at a pressure of 20 lb./in.’ by an Arndorfer constant infusion pump (Arndorfer Instruments, Greendale, Wis.), pressures were recorded by Statham P23 series transducers (Statham Instruments, Hato Ray, Puerto Rico), and the write-out was on a Beckman R611 Dynograph (Beckman Instruments, Fullerton, Calif.). This recording system showed low compliance with sudden occlusion producing a rise of 600 cm H,O/s. The tube was passed by mouth and positioned fluoroscopically with the tip in the third part of the duodenum; the tube was fixed at the patient’s mouth. The proximal side hole recorded gas-
4
3
Number of contractions” Gb 0 0 0 DIG Dz D, D4
Mean Gb D,” D, D, D,
2
112
0 0 0 2 0 12 0 0 0 4 0 13 0 0 210 0 3 1 0 0 0 9 1 1 0 0 0 3 13 Mean=3flSD Mean = 32 f amplitude of contractions (cm H,O) 0 0 0 0 0 0 22 0 10 11 0 0 0 10 0 10 13 0 0 15 19 0 7 13 0 0 0 18 6 8 0 0 0 9 18 Mean = 10 f 2 cm Hz0 SD Mean = 11 f
3
4
4 0 7 10 8 8 6 16 8 6 13 SD 40 8 10 10 12 3 cm
5
2 5 10 10
0 29 5 0 6 8 12 15 10 16 H,O SD
0 Only counting contractions >5 cm HZO. b G = gastric contractions.= D,_, = duodenal contractions from proximal to distal.
July 1981
ABNORMAL MOTILITY IN MYOTONIC DYSTROPHY
motor complex (Figure 2). This complex occurred 57 min after the first complex was recorded (this subject’s usual period between complexes was not determined). The duration of maximal activity in the duodenum was 4 min 16 s (normal: 6 min 21 s f 2 min 19 s SD) (19), followed by a 9-min 13-s period of inhibition of motor activity (normal: 9 min 50 s + 5 min 11 s SD) (19). The time taken for the complex to travel 1 cm was 12.5 s (normal 9.9 + 6.4 s SD) (19).
Table
Response to Edrophonium Edrophonium HCl, given 23 min after the start of pentagastrin injection, was followed by an increase in the number and amplitude of duodenal contractions (see Table 2); edrophonium did not affect gastric antral contractions. Response to a Liquid Meal Sustacal of gastric antral the number of same response trols.
was followed by the disappearance contractions and a slight increase in duodenal contractions. This is the as observed in several normal con-
Maximal Rate of Contractions The contraction rate was counted when maximum contractile activity occurred, in order to estimate the rate of electrical control activity. This maximal activity was considered present when there was a persistent regular pattern of contraction, without dropped contractions. This occurred sometimes
2.
Motor
Response to Edrophonium
Before edrophonium (min) __--
5
4
147
3
Number of contractions’ G” 1 1 0
After edrophonium (min)
.I_-
2
112
3
4
5
D,C
0
0
1
0 0
1 1
0 1
0 5
0 8
1 3
1 5
D,
0 0 0
0 0 0
1 0 0
1 2 0
1 0 1
3 4 3
1 9 7
0 16 0
1 4 5
1 7 3
16 17 16 14 15
31 19 21 9 30
D, D,
Mean=ZflSD Mean = 24 + 19 SD Mean amplitude of contractions0 (cm H,O) G” D,’ D, D:, D,
111 0 Q 0 0
109 0 0 0 0
0 10 7 0 0
0 0 15 8 0
96 5 7 0 9
Mean = 10 rt 4 cm Hz0 SD
0 5 17 15 42
0 20 13 9 17
0 25 0 12 0
Mean = 18 f 6 cm H,O SD
” Including only contractions >5 cm HZO. b G = gastric contractions.” D1_4= duodenal contractions from proximal to distal.
during intermittent motor activity and always during a migrating motor complex. The maximum rate of contraction was then calculated as the inverse of the duration from the onset of one contraction to the onset of a subsequent contraction (the number of contractions counted ranging from 5 to 38 in the duodenum) and expressed as the number of contractions per minute. Similar values were calculated when the contraction rate was measured from the point of maximal amplitude of one contraction to that of a subsequent contraction. The duodenal contraction rates during maximal activity were as high as 18.5/min and as low as ll.O/min. The results at
Figure 2. Response of the stomach and duodenum to injection of pentagastrin, 0.3 /&kg i.v. The orrows indicate the injection of pentagastrin. R = respiration, G = gastric, D,-D, = duodenal recording sites from orad to aborad. The black dots mark artifacts in the record. A migrating motor complex commences 5 min after the injection of pentagastrin.
148
LEWIS AND DANIEL
GASTROENTEROLOGY
Table 3. Maximum Contraction Rate” Occurring at Each Recording Site
Basal Gastric Duodenal 1’
17.8(5)b
Duodenal 2
11.5(9)
Duodenal 3
17.1(5), 17.5(7), 16.7(5)
Duodenal 4
11.2(38)
Postpentagastrin 3.8(3)b 15.3(11), 11.1(18) 18.6(8), 11.8(10), 14.4(6) 16.7(12), 11.7(17)
17.4(11), 11.4(23)
Postedrophonium
12.2(6) -
lLO(10)
-
Postsustacal
16.2(7)b
12.9(12), 11.7(7), 15.7(11), 16.2(5), 14.2(y), 14.4(6), 13.7(9), 18:5(8) 17.8(12)
a Contractions per minute. b The numbers in parentheses indicate the number of contractions that were counted to calculate the contraction rate. c Duodenal l-4 signify the position of the recording site within the duodenum from orad to aborad.
each site seen did drugs or odenum, complex.
are shown in Table 3. The contraction rates not appear to be related to the effects of food, to the site of recording within the duor to the presence of a migrating motor
Discussion In dystrophia myotonica, abnormal esophageal (l-7) gastric (7-g), small bowel (X1-13), and coionic (7,16) motor dysfunctions have been described. Our studies showed abnormal motor function of the esophagus, stomach, duodenum, and colon. The involvement of cholinergic nerves in the production of disordered gastric and duodenal function was investigated by studying the effects of a meal, pentagastrin, and edrophonium. The motor activity intiated by a meal involves vagal activity (20). Edrophonium acts by preserving acetylcholine released by nerves, and pentagastrin by releasing acetylcholine from nerves in vivo (21,22). The meal produced the usual pattern of change in motor activity which we observe. Edrophonium increased duodenal but not antral motility as in our normal subjects (19). Pentagastrin increased antral and duodenal motility as in normal subjects (21). Soon after its injection, a migrating motor complex was seen; this was unlikely to be spontaneous as pentagastrin usually inhibits such complexes (23-25) but possibly triggered by the cessation of pentagastrin effects as in dogs (24). (Pentagastrin would be expected to have a shorter plasma half-life than gastrin-17, which is 6
Vol. 81, No. 1
min [26].) These data, as Well as morphologic studies of other such patients (27), indicate that cholinergic nerves may be structur$ly and functionally normal (within the limits of the procedures). (Function of inhibitory nerves was not. examined in this study.) The major abnormality of motor function we observed was an increased (up to- 18.5/min) and variable (down to Wmin) maximal rate of contraction in the duodenum. As the maximal rate of duodenal contraction is normally controlled by the maximum rate of electrical control activity (ECA) (28) this implies an increase in ECA frequency. If our duodenal probes sometimes did not record a contraction because in the dilated duodenum it failed to occlude the lumen, this would suggest that the ECA rate is even faster than the ma&mum contraction rate recorded. Our records do not suggest that missed contractions were occurring. The simplest hypothetical explanation for increased ECA frequency is a partial depolarization of duodenal smooth muscle cells resulting from damage to smooth muscle (increased leakiness to Na’ and/or Ca’+), with decreased activity of membrane electrogenic ion pump (similar changes to that seen in skeletal muscle [29]). It is conceivable that each probe recording duodenal contraction may in this case have been picking up activity initiated from a region large enough to include more than that occupied by a single electrical control wave. This is possible in this case as his ECA appeared to be unphase-locked, as judged by the varying contraction frequencies at adjacent sites. As a result of this, a higher frequency of lower amplitude contractions might be recorded; however, the regularity of contraction (during periods when contractions occurred at the maximum rate) would make this unlikely. The evaluation of these hypotheses will require direct electrophysiologic study of ECA and of membrane potentials in smooth muscle cells from such a patient. Increased ECA frequency could account for the absence of phase-locking (varied contraction frequencies in the duodenum at a given time) in the duodenum. This would occur if the frequencies of some pacemakers exceeded the ability of many regions to follow (28). Lack of continuous phase-locking of the duodenum could account for the variable gastric emptying shown by this patient as duodenal contents may not be rapidly cleared during periods of unlocking (peristaltic spread of contractions would be absent). Although we only,recorded from one antral site, this phenomenon could also be present intermittently within the stomach and could account for the vomiting. An alternate explanation for the failure of phase-locking in the duodenum is damage to cell-to-cell coupling (which may explain in part the loss of esophageal peristalsis [30]). This pos-
July1981
sibility could be evaluated by functional and structural studies of duodenal muscle. In conclusion, disordered gastrointestinal motility was widespread in a patient with dystrophia myotonica. The most striking changes were increased frequency and absence of phase-locking of the phasic contractions of the duodenum. These might result from damage to and depolarization of smooth muscle cells and could contribute to or be responsible for the vomiting that occurred.
ABNORMAL MOTILITY IN MYOTONIC DYSTROPHY
17.
18.
19.
20.
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