Changes in the pharyngeal and esophageal musculature in oculopharyngeal muscular dystrophy

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  • Changes in the Pharyngeal and Esophageal Musculature in Oculopharyngeal Muscular Dystrophy Report of 2 Cases


    o CULOPIIARYNGEAL Mt:SCULAR DYSTROPHY is characterized by slowly progres- sive ptosis and dysphag!a, which usually begins ill late adult life. Some

    patients also develop weakness of facial, extraocular, masticatory, and limb girdle musculature. Familial t-12 and sporadic ~-z, 1_~-16 cases have occurred; the former is inherited through an autosomal dominant gene. Difficult), in clear- ing the barium meal from the pharynx has been demonstrated radiograph- ically.4, 5,7,9, 1~-~3, ~ Motility studies have disclosed weakness in the motor function of both the pharynx and esophagns, v-', ~ the entire esophagus, '~, v-, or the upper third of the esophagus only. u

    Histologic evidence of involvement of the pharyngeal musculature by muscular dystrophy has been documented in 2 patients with oculopharyngeal muscular dystrophyS, ~ One was found following biopsy of the cricopharyn- geus at the time of cervical esophagomyotomy, 7 and the other at necropsy. ~2 The changes of muscular dystrophy have not, to my knowledge, been described in the esophagus of patients with this myopathy.

    This paper presents the histopathologic alterations of the pharyngeal and esophageal mtlsculature in 2 patients with octdopharyngeal muscular dys- trophy.


    A 75-)c:n-nld man was admiucd Io our hospilal on July 13, 1968 for exaluation of weight loss, increasing anorexia, weakness, and difficulty in swallowing which he had suffered for a period of 4-5 months. The patient as well as his mother, grandfather, and brother all had had bilateral ptosis and ditficuhv in swallowing for many )'cars. Physical examinat ion disdosed an elderly, poorl) nourished, weak, Spanish-Anaerican man with prominent ptosis. Regurgitat ion o[ fluid through the nose and coughing [ollowed his dr inking a gla~s of water. The oral mucosa was pale, and the tongue was not remarkable. The musculature of the extremities wa~ moderately wasted, and the neurological examinat ion was within

    From tbc Department of Pathology. Veterans Administrat ion Ilospital, al~d from the University of New Mexico School of Medicine, A lbuquerque.

    Presented at the Scientific Session of the Annua l Meeting of the Amcricau Society of Clinical Pathologists, Sept 14-21, 1969, Chicago, I11.

    Address for reprint requests: Dr. Weitzucr. V. A. Hospital, 200 Ridgco'cst Drive, SE, .'albuquerque, NM 87108.

    New Series, VoL 14, No. I I , 1969 ~0~

  • Weifzner

    normal limits. The clinical impression was oculophar)ngeal muscular d)strophy. Chest roentgenograms disclosed fibrotic lung fields. Ti le patient had difficulty ill swallowing bar ium into and beyond the upper esophagus. An upper gastrointestinal series, performed bx instil l ing air in bar ium through a nasogastric tube, revealed a carcinoma on the greater curvature of the body of the stomach. Electromyography and lnotility studies were not performed. A gastroenterostomy was performed; biopsy of the gastric mass was interpreted as adenocarcinoma. The patient developed increasing respiratory distress following surger} and expired on the third postoperative da).

    The major findings at autopsy were adenocarcinoma of the stomach and secondary adenocarcinoma in li~er, thoracic and luml)ar vertebrae, and perigastric lymph nodes. Other findings included octdol)fiarxngeal muscular dystroph.~ with imo lvement of tongue, pharynx, striated nmsclc of upper esophagus and deltoid, as well as bilateral lobular pneunionia, and pu lmonary emphysema and fibrosis.

    Microscopic examinat ion of the phar}nx and upper esophagus showed considerable variation in lhe caliber of their striated muscle fibers, an occasional hvalinized nmscle tiber. and increase of sarcolemmal nt=clei--some of which were centrally located. The interstitial fibrous connective tissue uas somewhat increased and edematous, hut adipose tissue was absent (Fig 1 and 2). The smooth nmscle of various levels of the esophagus was preserved and not significantly altered when compared Io that of several patients in tim sanre age group without oculophar.xugeal muscular dystrophy. There was also prominent adipose tissue replacement of the l ingual musculature. The brain, spinal cord, and peripheral nerves were essentially not renlarkahle.

    Case 2

    A 74-year-old man was admitted to our hospital on Feb 1, 1968 for weight loss, weakness. aml difficulty in s~-allowing. The patient had had bilateral ptosis for 16-I7 u~ars and dysphagia for about 1 ,,ear. l ie had difficulty in swallowing saliva and had choking spells at night. Luetic heart disease was diagnosed in 1966. His father anti daughter both had ptosis. Phxsical examinat ion disclosed a weak. emaciated. Spanish-American man with bilateral ptosis and dithcultv in swallowing sali~.t. The patient had a coughing spell after dr ink ing a glass of water. The jaws and tongue moxed well. There was a Grade II diastolic murmur of aortic insufficiency. T im thoracic aml l imb musculature was lnoderately wasted. The peripheral nervous sxstem was within normal linrits. The clinical impression was oculophar) ngeal muscular d}strophy and luetic heart disease. The patient had great difficulty in swallowing a bar imn meal. A small amount of bar ium passed into the esophagus, and the remainder was held up at the lower level of the inferior constrictor of the phar}nx. Some of the bar ium was aspirated into the trach~obronchial tree. Electro- myograph} and moti l ity studies were not performed. A cl icopharyngeal m.votomy was performed on Feb 16, 1968 with little i lnprovement in swallowing. The patient developed pneumonia several days later, followed shortly thereafter by hematemesis and melena. Ligation of the bleeding gastric arters, ~agotomy anti p sloroplasty were performed on March 7. 1968. T im patient de~eloped recurrent bouts of aspiration pneumonit is and expired on the fifteenth postoperative day.

    The major findings at autopsy were chronic gastric ulcer, aml oculopharyngeal muscular dystrophy with involvement of the tongue, phar )nx , striated muscle of upper portion of esophagus, temporalis, sternocleidomastoid, deltoid, and pectoralis major. Other findings included lobular pneumonia with organization, tuberculosis of the right upper lobe, imhnonary emphysema and fibrosis, and luetic mesaortitis.

    Histologic examinat ion of the phar~,nx and esophagus revealed prominent variation in the size of their striated inuscle fibers, occasional hvalinized nluscle fil)ern, and all increase of sarcolemmal nucle i - -some ol which were cenlrallv located. The interstitial fibrotts connectixe tissue was xariablv increased and edematous, but fret' of adipose tissue (Fig 3).

    806 American Journal of Digestive Diseases

  • Fig 1 (top). Section of upper portion of the esophagus in case 1 showing slriated muscle (ie[t) and smooth mnsclc (right). Striated muscle fibers ~arv considerably in caliber. Interstitial fibrous connective tissue is increased and edematous. Smooth muscle fibers are not remarkable. (H & E. X .,1.2) Fig 2 (bottom). Striated muscle of pharynx in case 1 showing increase of sarcolemmal nuclei, several of which are centrally located. (H g E, 64)

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    Fig 3. Typical area of striated musculature of pharynx and upper esophagus in Case 2 showing prominent variation in size of striated muscle fibers, increase of sarcolemmal nuclei, several of which are centrally located, and edematous interstitial tissue. (H g.: E, x 100)

    The smooth muscle of tile esophagus was essentiallx not remarkable. The lingual musculature was replaced by adipose tissue, but to a somewhat lesser degree than in Case 1. The central ncrxous system was free of luetic in~ohement. The brain, spinal cord, and peripheral ntrves were essentially not remarkable.


    T im h is topatho logy of the str iated muscu lature of tim pharynx, upper third of the esophagus, and other muscles examined in both pat ients were typical of muscular dystrophy. Carc inomatous myopathy may be excluded in the first pat ient because the ptosis and dysphagia were present for many years, and the str iated muscu lature examined showed dyst rophy rather than nonspecific changes. Accord ing to Drachman et al, ~r the microscopic features at t r ibuted io myopathy (muscular dystrophy and myotonic dystrol)hy ) may occur in pure par t ia l denervat ion (pol iomyel i t is) of long standing. They also believe that it is not clear whether the nerve or muscle is the pr imary site of involve- ment in muscular dystrophy. In the 2 cases reported, it can I)e safely assumed that the muscular changes represent a 1)rimary muscular process, because tim brain, the spinal cord, and per iphera l nerves were essential ly normal.

    I t is unfor tunate that mot i l i ty studies were not per formed in e i ther pat ient.

    808 American Journal of Digestive Diseases

  • Muscular Dystrophy

    The smooth must le of tile esophagus in both, however, was not signif icantly altered histopathological ly , when compared to several pat ients in the same age group wi thout ocu lopharyngea l muscu lar dystrophy. In Roberts and Bam- forth's pat ient with this myopathy, ~-~ the pharynx was involved, but the esophageal smooth muscu lature was normal . The h is topathology of the str iated muscle of the ul~pet' esophagus was unfor tunate ly not inc luded in the necropsy report.

    I t is, therefore, postu lated that the dysphagia in the 2 castes of repor ted ocu lopharyngeal muscular dystrophy, and most probably , Roberts and Bam- forth's pat ient as well, resulted fi'om the changes of ntuscular dystrophy affecting the sn ia ted muscu lature of tile pharynx and upper por t ion of the esophagus. Th is supports Murphy and Drachman's n conclusion based on deglut i t ion studies, that the abnormal i ty in swal lowing in this condi t ion is confined to the pharynx, and upper esophagus.

    Mot i l i ty studies in several pat ients with oculophztvyngeal muscular dystro- phy have ind icated diffuse weakness o{ tile esophagus. ~, ze. 1~ Th is is difficult to explain, but it is possible that the esophageal smooth muscu lature in these pat ients may have undergone at rophy and size var iat ion and dropp ing out of fibers, as Bevztns ~s describes several pat ients with progressive muscular dys- trophy.


    Two pat ients wi~h ocu lopharyngea l muscular d vstroplly, in whom the pharynx and esophagus were examined at necropsy, are presented. I t is postu- lated that the dysphagia in both resulted from the histologic changes of muscular dystrophy which affected the str iated muscu lature of the pharynx and upper esophagus.

    REFERENCES 1. T~rol~, E. x,V. ProgJessixe vagus-glossopharvngeal paralx~is with ptosis: Contribution

    to a group of family diseases. I Ne~, Me~t Dis 42:129, 1915. 2. AMYOT, R. IIereditary. familial and acquired pto,~is of late-onset. Canad Meal Ass 1

    59:434, 1948. 3. S.~UCnCR, J. The clinical significance of ptosis with special reference to ptosls of late

    onset, f Nerv ate~t Dis 119:148, 1954. -t. LUNDBFRC,, P. O. Ocular myopathy with hypogonadism. Acta Neurol Stand 3&142, 1962. 5. VmToa, M.. tt.~x'vs, R., and AD..~XtS, R. D. Ocutopharyngeal muscular dystrophy: A

    familial disease of late life characterized by d~sphagia and progressive ptosi~ of the eyelids. New Eng J Med 267:1267, 1962.

    (i. HAYES, R., LONDON, IV., SEIDMAN. J., and EStBa~F, I.. Oculopharyngeal muscular dystrophy. New Eng .1 Med 268:163, 1963.

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    ~. ,~CHO|I.-kND, l). L., and ROXVI,AND, L. P. -Muscular dystrophy. Arch NeuroI 10:433. 1964. 9. BRAY. G. M., K.*ap, soo. M., and Ross. R. T. Ocular myopathy with dysphagia. Nemologv

    (Minneap.) 15:678, 1965, I0. S>,TO','OSHI, E., ~,[UR.*.K~-MI. K.. KOWA. H., KISOSHITA..XI., and ToRm J. Distal involvement

    of the extremities in ocular myopathy..4met f Ophthal 59:668, 1965. 11. MuRpm', S. F., and DRACHM3.N.D. lg. The oculopharyngeal syndrome, lAMA 203.'1003,


    N6,w Series. Vol. 14, No, I I , 1969 809

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    12. ROI3E~TS, A. H., and BAMFORrH, J. The phar}nx and esophagus ill ocular muscular dystrophy. Neurology (Minneap.) 18:645, 1968.

    13. L~,rs. F., and LIVERSED~.I:. L. A. Descending ocular m~opathy Brain 85:701, 1962. 14. q'EASOALL. R. I)., SCHuSrrR. M. M., and WALSri. F. B. Sphincter involvement in ocular

    myopathy. Arch Neuro[ 10:446, 1964. 15. Lr:wls, I. I,ate-onset musctdar dystrophy: Oculophar}ngoesophageal xariety. Canad Med

    Ass J 95:146, 1966. 16. ELLIs, J. G,, DAt,r_sslo, D. J.. and Lowi , H. M. Ocular myopathy: Disease of muscle in

    tbe elderly. :liner J Olhltml 61:167, 1966. i7. DRACH:qA,',, 1). B., MVRPH:'. S. R.. NIc, xxi. M. l'.. and Hn~t,s, J. R. "M~opathic'" changes

    in chronically denervated muscle. _41~h ,Velttol 16:14, 1967. 18. BEVAN~, .XI. Challgcs in the musculature of the gastrointestinal tract and in the

    , 40 . . . . . 1945. mvocardium in progressive muscular dystrophy. Arch Path '95

    8"t0 American Journal of Digestive Diseases


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