Esophageal Motor Function in Patients With Muscular Dystrophy

Transcription

1 GASTROENTEROLOGY 1986;9: Esophgel Motor Function in Ptients With Musculr Dystrophy VOLKER F. ECKARDT, WILFRIED NIX, WERNER KRAUS, nd JURGEN BOHL Gstroenterologisches Institut Wiesbden, Neurologische Klinik, Nuklermedizinische Abteilung, Abteilung fur Neuropthologie, Universitiit Minz, Federl Republic of Germny In study designed to evlute esophgel motor function in musculr dystrophy we exmined 13 ptients with myotonic dystrophy, 14 ptients with "nonmyotonic" musculr dystrophy, nd 8 helthy control subjects by mnometric nd rdionuclide trnsit studies. Ptients with myotonic dystrophy exhibited mrked wekness of esophgel contrctions nd upper esophgel sphincter pressure. Coordintion of sphincter relxtion nd peristltic sequences remined unltered. These chnges led to delyed esophgel emptying in ll pqtients with myotonic dystrophy. Although esophgel function ws lso impired in the distl esophgus, on histologic studies, morphologic ltertions were confined to esophgel strited muscle in single ptient with myotonic dystrophy. In contrst to the mrked dysfunction of esophgel motility in ptients with myotoni, no such ltertions were observed in the "nonmyotonic" form of musculr dystrophy. Ptients with myotonic dystrophy (MD) frequently complin of symptoms relted to the gstrointestinl trct (1). Although strited nd smooth muscle bnormlities hve been demonstrted nywhere from the phrynx to the nl sphincter, most gstrointestinl symptoms cn be ttributed to esophgel dysfunction (2-4). Rdiogrphic studies in these ptients hve reveled disorders of phryngel emptying s well s bnorml nd ineffectul peristlsis throughout the esophgel body (3-6). These findings were substntited by erly mnometric investigtions demonstrting vrious motor bnormlities of the phrynx nd esophgel body (2,4,6-9). The conclusions Received December 3, Accepted September 16, Address requests for reprints to: Prof. Dr. Volker F. Eckrdt, Dotzheimer Strsse 14-18, 62 Wiesbden, Federl Republic of Germny by the Americn Gstroenterologicl Assocition /86/$3.5 drwn from these studies, however, re limited in tht neither rdiogrphic studies nor the previously utilized mnometric systems llow ccurte quntifiction of esophgel nd phryngel motor ctivity (1).. The ims of this study were to define the esophgel motor bnormlity in ptients with MD using modern mnometric techniques nd to evlute whether similr chnges occur in "nonmyotonic" musculr dystrophies (NMDs). Furthermore, by using scintigrphic technique, we investigted whether the motility disturbnce in MD interferes with esophgel emptying. Mterils nd Methods Studies were performed in 13 ptients with MD, 14 ptients with NMD, nd 8 helthy volunteers. Ptients with NMD could be further subdivided into 5 ptients with fcioscpulohumorl dystrophy, 7 ptients with limb-girdle dystrophy, nd 2 ptients with scpuloperonel dystrophy. Ptients with MD hd men ge of 44.9 ± 2.4 yr (men + 1 SE), which ws similr to tht of ptients with NMD (35.9 ± 3.2 yr) nd norml control subjects (36.8 ± 2.4 yr). Written informed consent ws obtined from ll subjects nd the reserch ws crried out ccording to the Declrtion of Helsinki. Clinicl nd Neurologic Assessment of Ptients The dignosis of musculr dystrophy ws bsed on clinicl, genetic, nd electrophysiologicfindings. In ddition, muscle biopsy ws performed nd reveled dystrophic chnges in skeletl muscle in t lest one member of ech kinship. Slit lmp exmintion reveled myotonic ctrcts in ll ptients with MD. Myotoni could be demonstrted by clinicl exmintion nd during electromyogrphy. Nerve conduction studies excluded concomitnt peripherl Abbrevitions used in this pper: MD, myotonic dystrophy; NMD, nonmyotonic dystrophy.

2 Mrch 1986 ESOPHAGEAL FUNCTION IN MUSCULAR DYSTROPHY 629 nerve disese. Crdiovsculr exmintion disclosed mitrl vlve prolpse in 7 ptients nd electrocrdiogrphic conduction bnormlities in nother 7 ptients. Nonmyotonic muscle disorders such s fcioscpulohumorl (5 ptients), scpuloperonel (2 ptients), nd limb-girdle (7 ptients) dystrophy were primrily dignosed by the distribution of the ffected muscles nd muscle biopsy findings. Mnometric Studies With the exception of 1 ptient with MD nd n dditionl ptient with fcioscpulohumorl dystrophy, ll ptients nd controls underwent esophgel mnometry. Pressure mesurements of the lower esophgel sphincter nd esophgel body were performed using tube ssembly consisting of three ctheters with n internl dimeter of 1.4 mm nd lterl orifice of 1.2 mm. Ech ctheter ws perfused with distilled wter t.5 mllmin with low-complince pneumohydrulic cpillry infusion system (Mui Scientific, Toronto, Cnd), which hd pressure rise rte of 4 mmhg/s. The pressure recording ctheters were rdilly oriented t 12 ngles nd were rrnged to mesure intrluminl pressure t three oints 5 cm prt. Intrluminl pressures were trnsmitted to externl trnsducers (model P23, Stthm, Oxnrd, Clif.) nd directly trced on Rikdenki multichnnel recorder. Pressure mesurements of the upper esophgel sphincter were performed with n ovl-shped, four-lumen ctheter tht hd n externl dimeter of 4 x 6 mm. The recording orifices were rdilly oriented t 9 ngles nd were locted t the sme cross-sectionl level. All studies were performed fter 12-h fsting period nd while the subject ws resting quietly in supine position. Upper esophgel sphincter pressure ws determined first using the ovl-shped ctheter. After the tube ssembly ws positioned in the upper esophgus, it ws then withdrwn in.5-cm segments from the esophgus into the phrynx. Pressures were recorded for 1 s fter ech withdrwl. Upper esophgel sphincter pressure ws determined s the men of two complete pullthroughs. Although pressure recordings were obtined in the nterior, posterior, nd in both lterl positions, posterior upper esophgel sphincter pressure ws used for sttisticl clcultions. Lower esophgel sphincter pressure mesurements were performed using n identicl pull-through technique s described for posterior upper esophgel sphincter pressure mesurements. In ech ptient two complete pull-throughs were performed, representing six individul determintions. To record completeness of relxtion of the lower nd upper esophgel sphincter, the tube ssembly ws positioned nd nchored with the distl pressurerecording orifice t the point of mximl pressure nd the proximl side hole 5 cm bove the lower nd upper esophgel sphincter. Peristltic ctivity ws mesured over the entire length of the esophgel body. The mnometric tube ws positioned first t 2.5 cm proximl to the lower esophgel sphincter nd then ws withdrwn t 2.5-cm intervls until the distl recording orifice hd reched the upper esophgel sphincter. At ech sttion, subjects were sked to perform six wet swllows by dministering 5-ml bolus of wter t room temperture into the mouth from syringe. All swllows were seprted by 3-s intervls during which no esophgel contrctions occurred. The mplitude of esophgel contrctions ws mesured s the difference between the esophgel bseline nd the pek of the contrction wve. The durtion of the contrction wve ws mesured in seconds from the onset of mjor upstroke to the end of contrction wve. For ech sttion the men mplitude nd durtion of esophgel contrctions were clculted. However, to permit pooling of dt from different subjects, the esophgus ws divided into proximl, middle, nd distl third nd sttisticl clcultions were bsed on the men vlues of ll contrctions in ech third. The velocity of esophgel peristlsis ws mesured s the time difference between the contrction peks t two different recording points. All trcings were nlyzed for the occurrence of repetitive, nonperistltic, nd "dropout" contrctions. Repetitive contrctions were defined s those in which single swllow ws followed by three or more consecutive wves, wheres "dropout" contrctions were defined s complete bsence of esophgel motor ctivity following wet swllow. Scintigrphic Studies In 12 ptients with MD, 2 ptients with fcioscpulohumorl dystrophy, nd ll control subjects, rdionuclide trnsit ws determined ccording to the method of Russell et l. (11). The fsting subjects were positioned supine with their chest under the collimtor of 'i-cmer (Dyn Cmer 4c, Picker Compny, Northford, Conn.), which ws linked to Gmm 11 computer system (Digitl Equipment Corp., Mynrd, Mss.). A rdioctive mrker ws tped to the neck t the level of the cricoid crtilge nd rdioctivity ws mesured over n re covering the neck, chest, nd upper bdomen. After the subjects swllowed bolus of 1 ml of wter contining 25 Ci of 99ffiTc_sulfur colloid, recordings were obtined for the following 2 min. Rdioctivity dt were stored t.5-s intervls during the first minute nd t l-min intervls for the remining period of 19 min. For quntittive evlution of the stored dt, regions of interest were plced over the entire esophgus, three different esophgel regions (proximl, middle, nd distl third), nd the stomch. Esophgel emptying curves were constructed by plotting the percentge of rdioctivity lost on the ordinte ginst time on the bsciss. Histologic Studies Light microscopic studies were performed on mteril obtined t utopsy from n dditionl ptient with MD who died of spirtion pneumoni. Multiple trnsverse sections were obtined from different levels long the entire length of the esophgus. Ech 4-m section ws stined with hemtoxylin nd eosin nd denosine tri-

3 63 ECKARDT ET AL. GASTROENTEROLOGY Vol. 9, No.3 CI :I: Erb FSHD *SPD e15 e -r. Ir 1 * ::::>... * 5 &1...1& Control MD NMD Figure 1. Posterior upper esophgel sphincter pressure (PUESP) in ptients with myotonic nd nonmyotonic musculr dystrophy nd controls. Erb, limb-girdle dystrophy; FSHD, fcioscpulohumorl dystrophy; SPD, scpuloperonel dystrophy. phosphtse. The ltter stin ws used to llow differentition between type I nd type II fibers of esophgel strited muscle. Muscle fiber size ws mesured on cryostt sections, wheres morphologic studies were performed on hemtoxylin nd eosin preprtions. The fiber size distribution of esophgel strited muscle ws quntittively ssessed by constructing histogrms. For comprison, identicl studies were performed on mteril obtined t utopsy from ptient of similr ge who hd died of crdiovsculr disese nd who hd no evidence for neurologic or musculr illness. Sttisticl Anlysis The Mnn-Whitney U-test nd the Student's t-test were used in the sttisticl nlysis of the dt. Probbility vlues were corrected ccording to Bonferroni in the single cse where multiple t-tests hd to be pplied. Results Esophgel Symptoms On detiled questioning, 5 ptients with MD described symptoms referred to the phrynx or esophgus. One ptient complined of orophryngel dysphgi nd 2 ptients described the occsionl senstion of food sticking behind the sternum. Two ptients with MD complined of frequent episodes of hertburn, which ws combined with occsionl dysphgi in 1. A single ptient with fcioscpulohumorl dystrophy complined of orophryngel dysphgi, nd nother ptient with limb-girdle dystrophy hd frequent episodes of hertburn. Brium studies of the esophgus were performed in ll 7 symptomtic ptients nd were interpreted s being norml. There ws no evidence for diverticul or neoplstic or inflmmtory lesions of the esophgus. Upper Esophgel Sphincter Function Posterior upper esophgel sphincter pressure (Figure 1) ws mrkedly reduced in ptients with MD (2.8 ± 3.4 mmhg) compred with control subjects (17.5 ± 21.5 mmhg) (p <.1). However, tonic contrctions or impired relxtions, which re chrcteristic fetures of skeletl muscle in ptients with MD, were not observed in esophgel strited muscle. The percentge nd durtion of sphincter relxtion ws similr in ptients with myotoni nd controls. In ddition, the ndir of sphincter relxtion in ptients nd controls lwys occurred t the zenith of phryngel contrctions. When compred with norml subjects, ptients with MD reveled "fter swllow contrctions" of similr durtion but lesser mplitude (Figure 2), indicting tht "myotoni" does not occur in esophgel strited muscle. The degree of upper esophgel sphincter insufficiency ws not relted to the severity or durtion of the disese. As indicted in Figure 1, there ws little vrition in upper esophgel sphincter pressure. Upper esophgel sphincter pressures in ptients <4 yr of ge (men 15.5 mmhg) nd reltively short durtion of disese were similr to those in ptients >5 yr of ge (men 14. mmhg). In contrst to ptients with MD, ptients with NMD exhibited posterior upper esophgel sphincter pressures tht were comprble to those of the control group (Tble 1, Figure 1). Esophgel Peristlsis The mjority of wet swllows elicited propulsive contrctions in control subjects nd ptients 4 l : 11-5 g Mtonic Dystrophy Control Phrynx * 4 Esophgus! l n i.jppqr UES o Figure 2. Mnometric trcings from the phrynx nd proximl esophgus in ptient with myotonic dystrophy nd control subject. The ptient's trcing is chrcterized by decrese in upper esophgel sphincter (UES) pressure nd peristltic mplitudes. The rrows indicte swllowing.

4 Mrch 1986 ESOPHAGEAL FUNCTION IN MUSCULAR DYSTROPHY 631 Tble 1. Pressure Chrcteristics in Ptients With "Nonrnyotonic" Musculr Dystrophy Sphincter Contrction mplitude pressures (mmhg) (mmhg) Upper Middle Distl Ptients PUES LES third third third ERB Y.A O.H K.J.H G.K M.G A.K H.S FSHD H.M H.G.M H.P.M J.e SPD O.S E.G ERB, limb-girdle dystrophy; FSHD, fcioscpulohumorl dystrophy; LES, lower esophgel sphincter; PUES, posterior upper esophgel sphincter; SPD, scpuloperonel dystrophy. with musculr dystrophy. However, "dropout" contrctions were occsionlly observed in 5 ptients with MD nd 2 ptients with fcioscpulohumorl dystrophy. Abnorml contrctions (spontneous or repetitive) were extremely uncommon nd occurred only in 1 ptient with MD (13% of ll contrctions). Similrly, the velocity of peristltic contrctions ws comprble in ptients nd controls. The most significnt bnormlity of esophgel peristlsis ws mrked decrese in contrction mplitude in ll ptients with MD. As illustrted in Figure 3, the men contrction mplitudes of ptients with MD in the upper, middle, nd lower esophgus were 6.8 ±.7, 16. ± 1.8, nd 19.1 ± 2.5 mmhg, respectively, s compred with vlues of 5.2 ± 6.2, 83.5 ± 8.4, nd 95.1 ± 8.4 mmhg in control subjects. These findings were highly significnt for ll three thirds of the esophgus (p <.1). In ptients with MD the vrition in peristltic mplitude ws extremely smll, nd no correltion ws found between the durtion of the disese nd the height of contrction mplitudes. Although contrction durtion in the upper third of the esophgus ws slightly prolonged in ptients with MD (4.5 ±.4 s) compred with controls (3.5 ±.2 s), none of these differences reched sttisticl significnce. Among ptients with NMD, only those with fcioscpulohumorl dystrophy reveled mild decrese in peristltic mplitude, which ws most pronounced in the proximl third of the esophgus. C\ :I: 12 AErb FSHD *SPD 8 proximl _A_ A A..".,.. t third 4 * 8 A + C,g --- *' o 12 o -- c..>...".- 8 g * A A * distl A ""'II'"" 4 third Control MD NMD Figure 3. Contrction mplitudes in different esophgel regions in norml persons nd ptients with myotonic nd nonmyotonic musculr dystrophy. Erb, limb-girdle dystrophy; FSHD, fcioscpulohumorl dystrophy; SPD, scpuloperonel dystrophy. These ltertions, however, did not rech the degree of bnormlity observed in ptients with MD. Lower Esophgel Sphincter Function Figure 4 shows tht the men resting lower esophgel sphincter pressure in ptients with MD (12.3 ± 1.4 mmhg) ws not significntly different C\ :I: E 4 lj 2.. Vl A LU...I 1 A 12 o E.h ' A 2 -r- * middl!2 * third 4 A -c( _.- Control MD NMD Figure 4. Lower esophgel sphincter pressure (LESP) in ptients with myotonic nd nonmyotonic musculr dystrophy nd control subjects. Erb, limb-girdle dystrophy; FSHD, fcioscpulohumorl dystrophy; SPD, scpuloperonel dystrophy. AErb FSHD *SPD * *

5 632 ECKARDT ET AL. GASTROENTEROLOGY Vol. 9, No.3 from the lower esophgel sphincter pressure of controls (15.9 ± 1.2 mmhg) nd ptients with NMD (Tble 1). Complete nd coordinte sphincter relxtion ws observed both in ptients nd controls. Rdionuclide Trnsit In norml persons, the totl trnsit time of the swllowed bolus vried from 6 to 25 s nd ws terminted within 8 s in 7 of the 8 subjects. In contrst, only 3 ptients with MD hd emptied their esophgus within 2 min. As demonstrted in Figure 5, esophgel trnsit ws significntly delyed throughout the study period in ptients with MD. At.1, 1., 1, nd 2 min, esophgel emptying in ptients ws mrkedly diminished (48.9% ± 5.3%, 65.9% ± 6.1%, 73.8% ± 5.%, nd 76.9% ± 5.%, respectively) compred with norml controls (8.7% ± 4.8%, 96.8% ±.2%, 96.8% ±.2%, nd 96.8% ±.2%). These differences in esophgel trnsit reched sttisticl significnce for ech time intervl (p <.1,.1,.5, nd.5). The dely in trnsit ws observed in ll three thirds of the esophgus, but ws most pronounced in the distl third. The 2 ptients with fcioscpulohumorl dystrophy in whom rdionuclide studies were performed 1 REL. FREQUENCY e/ o 4 b 8 12 )1m Figure 6. Histogrms of strited muscle from the proximl esophgus. The upper prt () shows postmortem biopsy from ptient with myotonic dystrophy in comprison with control (b). In myotonic dystrophy the vrition of muscle fiber size is incresed nd the men vlue is higher thn in the control subject. reveled norml trnsit times (8.5 nd 13.5 s, respectively). In ddition, no bnormlities were found when trnsit times for ech third of the esophgus were nlyzed seprtely. Histologic Findings 2 o Controls Myotonic C trophy, men:!: 1SE time (min) Figure 5. Esophgel emptying of liquid bolus s mesured by rdionuclide trnsit studies in ptients with myotonic dystrophy nd controls. Cross sections of esophgel strited muscle from ptient with myotonic musculr dystrophy reveled mrked vrition of muscle fiber size with dimeters between 12 nd 118 /-Lm. As illustrted in Figure 6, men muscle fiber size in the ptient with MD (44 ± 14 /-Lm) ws incresed in comprison to the control subject (34 ± 7.5 flm).mny fibers hd internlimclei lind some showedpykhotic pluips. Furthermore, wheres severl fibers showed splitting nd necrosis, others were regenerting (Figure 7). In denosine triphosphtse preprtions, there ws no grouping of fiber types nd no fiber type predominnce. All ltertions were observed in both fiber types. There ws no evidence of inflmmtion, but some res reveled mrked prolifertion of dipose nd endomysil tissue. In contrst to the striking bnormlities ofesophgel strited muscle, no such ltertions were found in esophgel smooth muscle. At the light microscopic level, there ws no evidence of inflmmtion

6 ESOPHAGEAL FUNCTION IN MUSCULAR DYSTROPHY Mrch "1, ".. '!.- -.,, I..-..,... " I.,.,...,...,. I'. :,/ ;," " '; t ","; 633.' I I,,1,' 1 1 r.1 Figure 7. Esophgus from ptient with myotonic musculr dystrophy. In the proximl esophgus, the epithelium nd submucosl connective tissue ppers norml (), wheres esophgel strited muscle exhibits mrked bnormlities consisting of vrition in fiber size, internliztion of nuclei, nd occsionl fiber splitting nd necrosis (b). The distl esophgus revels n intct epithelium nd norml thickness of both lyers of the musculris propri (c). At the light microscopic level, no ltertions of circulr nd longitudinl smooth muscle were observed (d). (Autopsy mteril, formldehyde fixtion, embedding in prffin, H & E stining, originl mgnifiction x 16. The horizontl br represents 1 /-Lm.)

7 634 ECKARDT ET AL. GASTROENTEROLOGY Vol. 9, No.3 or degenertion. In ddition, the number nd size of nerve cells nd nerve fibers ppered to be norml. Discussion The findings of the present study confirm previous observtions tht ptients with MD exhibit mrked esophgel motility disorder (2-9). In ddition, however, the dt permit cler definition of the bnorml motor events nd comprison of these findings with those in p;:ltients with NMD nd helthy control subjects. In this study, musculr wekness of the upper esophgel sphincter nd esophgel body ws the predominnt motility disturbnce in ptients with MD. In contrst, evidence for neurl dysfunction s mnifested by bnormlities in completeness nd coordintion of sphincter rlxtion, or the ppernce of nonperistltic nd bnorml contrctions in the esophgel body, ws not detected in nyone of the ptients with MD. In regrd to sphincter relxtion, it cnnot be totlly excluded tht some recordings were rtifctul nd due to the movement of the pressure mesuring device during swllowing. However, the consistency of norml relxtions, the demonstrtion of "fter swllow contrctions," nd the norml proggtion of peristltic wves indicte tht the motility disturbnce in ptients with MD is relted to the musculr defect per se rther thn to neuromusculr chnges or ltered neurl trnsmission. The difference in results between this nd, previous investigtions (2,6,8) is most likely explined by the difference in experimentl procedures. Previous studies were performed with unperfused ctheters nd no considertion ws given to the rdil symmetry of upper esophgel sphincter pressure. In the current study, the use of high fidelity recording system nd n ovl-shped ctheter llowed ccurte determintion of the pressure events in the phrynx nd esophgus (1,12). The motor dysfunction observed in ptients with MD ppers to be unique for this disorder nd ws detected in vrying degrees in ech of the ptients studied. Among ptients with NMD, only those with the fcioscpulohumorl form showed mild decrese of the peristltic mplitude in the proximl esophgus. Esophgel trnsit ws norml, however, in the 2 ptients in whom this ws studied, nd no bnormlities in upper or lower esophgel sphincter function could be detected. Therefore, in contrst to ptients with MD, none of the subgroups of ptients with NMD reveled significnt bnormlities of esophgel motor function. In ech cse the results of esophgel function studies llowed cler seprtion between MD nd NMD. Although rdionuclide studies reveled the pres- ence of motility disturbnce in ech ptient with MD, we could not detect n emptying pttern tht would be chrcteristic for this disorder. In fct, some ptients with MD exhibited similr emptying curve s hs been reported for ptients with chlsi (13). Thus, rdionuclide trnsit studies represent sensitive screening test to detect esophgel motor dysfunction, but do not llow differentition between different motility disorders. In contrst, mnometric studies with modern techniques my disclose motility pttern tht is unique for ptients with MD. These ltertions exclusively consist of mrked decrese in upper esophgel sphincter pressure nd the mplitude of peristltic contrctions. As noted in previous investigtions (2,6), there ws no cler correltion between the severity of the disese nd the degree of esophgel motor dysfunction. Even mildly ffected ptients with short durtion of clinicl disese showed mrked bnormlities of esophgel motor function. With regrd to the extent of the motility disorder, it is surprising tht less thn hlf of the ptients complined of symptoms, which most often were only detected by detiled questioning. These differences cnnot be explined by lck of importnce of the contrction mplitude for bolus trnsit. Rdionuclide studies, which hve been shown to be sensitive test for the detection of bnormlities in bolus trnsit (11,13,14), were highly bnorml in ll ptients with MD. Perhps these ptients dpt slowly to the disturbnce of esophgel function, resulting in decresed perception of gstrointestinl symptoms. It hs been previously shown tht gstrointestinl smooth muscle function my be ltered in ptients with MD (15,16). Similrly, our ptients exhibited mrked dysfunction of the motor events in the distl esophgus where smooth muscle predomintes. These bnormlities consisted of significnt decrese in the peristltic mplitude, similr to the chnges observed in the proximl esophgus. Surprisingly, however, histologic exmintion reveled pthologicl findings tht were confined to esophgel strited muscle, wheres both lyers of the smooth muscle ppered norml. To our knowledge only one previous cse report exmined the esophgel muscle in ptient with MD. As in the cse reported by us, the uthors noted mrked trophy of strited muscle nd only minor chnges in esophgel smooth muscle (17). These differences between morphologic nd mnometric studies might indicte either tht severe morphologic chnges my remin unrecognized during light microscopic exmintion or tht the mplitude of distl esophgel contrctions is in prt function of the contrctile force originting in the upper esophgus.

8 Mrch 1986 ESOPHAGEAL FUNCTION IN MUSCULAR DYSTROPHY 635 References 1. Nowk TV. Ionsescu V. Anurs S. Gstrointestinl mnifesttions of the musculr dystrophies. Gstroenteroiogy 1982; 82: Grrett JM. DuBose TD. Jckson JE. Normn JR. Esophgel nd pulmonry disturbnces in myotoni dystrophic. Arch Intern Med 1969;123: Hughes DTD. Swmm JC. Gleeson JA. Lee IF. Abnormlities in swllowing ssocited with dystrophic myotonic. Brin 1965;88: Schumn BM. Rinldo JA. Drnley JD. Viscerl chnges in myotonic dystrophy. Ann Intern Med 1965;63: Simpson AI. Khilnni MT. Gstrointestinl mnifesttions of the musculr dystrophies. A review of roentgen findings. Am J Roentgenol Rdium Ther Nucl Med 1975;125: Hrvey JC. Sherbourne DH. Siegel CI. Smooth muscle involvement in rrtyotonic dystrophy. Am J Med 1965;39: Pierce JW. Cremer B. McDermot V. Phrynx nd oesophgus in dystrophic myotonic. Gut 1965;6: Siegel CI. Hendrix TR. Hrvey JC. The swllowing disorder in myotoni dystrophic. Gstroenterology 1966;5: Fischer RA. Ellison GW. Thyer WR. Spiro HM. Glser GH. Esophgel motility in neuromusculr disorders. Ann Intern Med 1965;63: Dodds WI. Stef JJ. Hogn WJ. Fctors determining pressure mesurement ccurcy by intrluminl esophgel mnometry. Gstroenterology 1976;7: Russell COHo Hill LD. Holmes ER. Hull DA. Gnnon R. Pope CEo Rdionuclide trnsit: sensitive screening test for esophgel dysfunction. Gstroenterology 1981;8: Gerhrdt DC. Shuck TS. Bordeux RA. Winship DH. Humn upper esophgel sphincter. Gstroenterology 1978;75: Gross R. Johnson LF. Kminski RJ. Esophgel emptying in chlsi quntitted by rdioisotope technique. Dig Dis Sci 1979;24: Tolin RD. Mlmud LS. Reilley J. Fisher RS. Esophgel scintigrphy to quntitte esophgel trnsit (quntittion of esophgel trnsit). Gstroenterology 1979;76: Nowk TV. Anurs S. Brown BP. ionsescu V. Green JB. Smll intestinl motility in myotonic dystrophy ptients. Gstroenterology 1984;86: Hmel-Roy J. Devroede G. Arhn P. Tetreult JP. Lemieux B. Scott H. Functionl bnormlities of the nl sphincters in ptients with myotonic dystrophy. Gstroenterology 1984; 86: Jequier M. Todorov A. Aspects nouveux de l mldie de Steinert. Rev OtoneuroophtlmoI1967;39:18-12.