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

STANLEY ~VEITZNIER, M D

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 T h e 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.

CASE R E P O R T S Case 1

A 75-)c:n-nld m a n was a d m i u c d Io our hospi lal on July 13, 1968 for exa lua t ion of weight loss, increasing anorexia , weakness, and difficulty in swallowing which he had suffered for a period of 4-5 mon ths . T h e pa t ien t as well as his mother , g randfa the r , and b ro the r all had had bilateral ptosis and ditficuhv in swallowing for m a n y )'cars. Physical e x a m i n a t i o n d isdosed an elderly, poorl) nour i shed , weak, Spanish-Anaerican m a n wi th p r o m i n e n t ptosis. Regurg i ta t ion o[ fluid t h r o u g h the nose and c o u g h ing [ollowed his d r ink ing a gla~s of water. T h e oral mucosa was pale, and the tongue was not remarkable . T h e m u s c u l a t u r e of the ext remi t ies wa~ modera te ly wasted, and the neurological e x a m i n a t i o n was wi th in

From tbc D e p a r t m e n t of Pathology. Veterans Admin i s t r a t ion I lospi tal , al~d from the Universi ty of New Mexico School of Medicine, A l b u que rque .

Presented at the Scientific Session of the A n n u a l Meet ing of the Amcr icau Society of Clinical Pathologists, Sept 14-21, 1969, Chicago, I11.

Address for repr in t requests: Dr. Weitzucr . V. A. Hospital , 2•00 Ridgco 'cs t Drive, SE, . 'albuquerque, N M 87108.

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

Weifzner

n o r m a l limits. T h e clinical impress ion was ocu lopha r )ngea l muscu la r d)s t rophy. Chest roen tgenograms disclosed fibrotic l u n g fields. Ti le pa t ien t had difficulty ill swallowing ba r ium into and beyond the u p p e r esophagus. An u p p e r gas t ro in tes t ina l series, pe r fo rmed bx inst i l l ing air in b a r i u m t h r o u g h a nasogastr ic tube, revealed a carc inoma on the greater cu rva tu re of the body of the s tomach. E lec t romyography and lnotility studies were not per formed. A gas t roen te ros tomy was per formed; biopsy of the gastric mass was in terpre ted as adenocarc inoma. T h e pa t ien t developed increasing respiratory distress following surger} and expired on the th i rd postoperat ive da) .

T h e ma jo r f indings at autopsy were adenocarc inoma of the s tomach and secondary adenocarc inoma in li~er, thoracic and luml)ar vertebrae, and perigastr ic l y m p h nodes. Other f indings inc luded octdol)fiarxngeal muscu la r dystroph.~ with i m o l v e m e n t of tongue, pharynx , str iated nmsclc of u p p e r esophagus and deltoid, as well as bi lateral lobu la r pneunionia , and p u l m o n a r y e m p h y s e m a and fibrosis.

Microscopic e x a m i n a t i o n of the p h a r } n x and uppe r esophagus showed considerable var ia t ion in lhe caliber of their s t r ia ted muscle fibers, an occasional hval inized nmscle tiber. and increase of sarcolemmal nt=clei--some of which were central ly located. T h e interst i t ial f ibrous connective tissue u a s somewhat increased and edematous , hu t adipose tissue was absen t (Fig 1 and 2). T h e smooth nmscle of var ious levels of the esophagus was preserved and not significantly altered when compared Io tha t of several pa t ien ts in tim sanre age g roup wi thou t oculophar .xugeal m u s c u l a r dys t rophy. T h e r e was also p r o m i n e n t adipose tissue rep lacement of the l ingual musculature. T h e brain, spinal cord, and per iphera l nerves were essentially not renlarkahle.

Case 2

A 74-year-old m a n was admi t t ed to our hospi tal on Feb 1, 1968 for weight loss, weakness. aml difficulty in s~-allowing. T h e pa t ien t had had bilateral ptosis for 16-I7 u~ars and dysphagia for abou t 1 ,,ear. l i e had difficulty in swallowing saliva and had choking spells at n ight . Luet ic hear t disease was d iagnosed in 1966. His fa ther anti daugh t e r bo th had ptosis. Phxsical e x a m i n a t i o n disclosed a weak. emaciated. Spanish-Amer ican m a n with bilateral ptosis and dithcultv in swallowing sali~.t. T h e pa t ien t had a cough ing spell after d r i n k i n g a glass of water. T h e jaws and tongue moxed well. T h e r e was a Grade II diastolic m u r m u r of aortic insufficiency. T i m thoracic aml l imb muscu l a tu r e was lnoderately wasted. T h e per iphera l nervous sxstem was wi th in n o r m a l linrits. T h e clinical impression was oculophar ) ngeal muscu la r d}s t rophy and luetic hear t disease. T h e pa t ien t had great difficulty in swallowing a b a r i m n meal. A small a m o u n t of b a r i u m passed into the esophagus, and the r e m a i n d e r was he ld up at the lower level of the inferior constrictor of the pha r}nx . Some of the b a r i u m was aspira ted into the t rach~obronchia l tree. Electro- myograph} and mot i l i ty s tudies were not per formed. A c l icopharyngeal m.votomy was pe r fo rmed on Feb 16, 1968 wi th little i lnp rovement in swallowing. T h e pa t ien t developed p n e u m o n i a several days later, followed short ly thereaf ter by hematemes i s and melena. Ligat ion of the b leeding gastric ar ters , ~agotomy anti p s loroplas ty were per formed on March 7. 1968. T i m pa t ien t de~eloped recur ren t bouts of aspira t ion p n e u m o n i t i s and expired on the f i f teenth postoperat ive day.

T h e ma jo r f indings at autopsy were chronic gastric ulcer, aml oculopharyngea l muscu la r dys t rophy with invo lvement of the tongue, p h a r ) n x , s tr iated muscle of uppe r por t ion of esophagus , temporal is , s ternocleidomastoid, deltoid, and pectoralis major. O the r findings inc luded lobular p n e u m o n i a with organizat ion, tuberculosis of the r ight uppe r lobe, i m h n o n a r y e m p h y s e m a and fibrosis, and luetic mesaort i t is .

Histologic e x a m i n a t i o n of the phar~,nx and esophagus revealed p r o m i n e n t var ia t ion in the size of their s tr iated inuscle fibers, occasional hval inized nluscle fil)ern, and all increase of sarcolemmal n u c l e i - - s o m e ol which were cenlral lv located. T h e interst i t ial fibrotts connectixe t issue was xariablv increased and edematous , bu t 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)

Weifzner

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.

C O M M E N T

T i m h i s t o p a t h o l o g y of the s t r i a t ed m u s c u l a t u r e of tim pha rynx , u p p e r th i rd of the e sophagus , a n d o the r muscles e x a m i n e d in bo th pa t i en t s were typica l of m u s c u l a r dys t rophy . C a r c i n o m a t o u s m y o p a t h y may be exc luded in the first p a t i e n t because the ptosis and d y s p h a g i a were p resen t for m a n y years, and the s t r i a t ed m u s c u l a t u r e e x a m i n e d showed d y s t r o p h y r a t h e r than nonspecif ic changes. A c c o r d i n g to D r a c h m a n et a l , ~r the mic roscop ic features a t t r i b u t e d io m y o p a t h y (muscu la r d y s t r o p h y a n d m y o t o n i c dys t ro l )hy ) may occur in p u r e p a r t i a l d e n e r v a t i o n (po l iomyel i t i s ) of long s tand ing . T h e y also bel ieve tha t i t is not c lear whe the r the nerve or muscle is the p r i m a r y site of involve- m e n t in m u s c u l a r dys t rophy . In the 2 cases r epo r t ed , it can I)e safely assumed tha t the m u s c u l a r changes r ep re sen t a 1)rimary m u s c u l a r process, because tim b ra in , the sp ina l cord, a n d p e r i p h e r a l nerves were essent ia l ly normal .

I t is u n f o r t u n a t e tha t m o t i l i t y s tudies were no t p e r f o r m e d in e i the r pa t ien t .

808 American Journal of Digestive Diseases

Muscular Dystrophy

T h e smooth mus t l e of tile e sophagus in both , however , was no t s igni f icant ly a l t e red h i s topa tho log ica l ly , when c o m p a r e d to several pa t i en t s in the same age g r o u p w i t h o u t o c u l o p h a r y n g e a l m u s c u l a r dys t rophy . In R o b e r t s a n d Bam- for th ' s p a t i e n t wi th this m y o p a t h y , ~-~ the p h a r y n x was invo lved , b u t the esophagea l smoo th m u s c u l a t u r e was no rma l . T h e h i s t o p a t h o l o g y of the s t r i a t ed muscle of the ul~pet' e sophagus was u n f o r t u n a t e l y no t i n c l u d e d in the nec ropsy repor t .

I t is, therefore , p o s t u l a t e d tha t the d y s p h a g i a in the 2 castes of r e p o r t e d o c u l o p h a r y n g e a l m u s c u l a r dys t rophy , and mos t p r o b a b l y , Robe r t s a n d Bam- for th 's p a t i e n t as well, r e su l t ed fi 'om the changes of n tuscu la r d y s t r o p h y affect ing the s n i a t e d m u s c u l a t u r e of tile p h a r y n x a n d u p p e r p o r t i o n of the esophagus. T h i s suppor t s M u r p h y a n d D r a c h m a n ' s n conc lus ion based on d e g l u t i t i o n studies, tha t the a b n o r m a l i t y in swa l lowing in t h i s c o n d i t i o n is

conf ined to the pharynx , a n d u p p e r esophagus . M o t i l i t y s tudies in several pa t i en t s w i th oculophztvyngeal m u s c u l a r dystro-

phy have i n d i c a t e d diffuse weakness o{ ti le esophagus . ~, ze. 1~ T h i s is diff icult to exp la in , b u t it is poss ib le tha t the e sophage a l smoo th m u s c u l a t u r e in these pa t i en t s may have u n d e r g o n e a t r o p h y a n d size v a r i a t i o n a n d d r o p p i n g o u t of fibers, as Bevztns ~s descr ibes several pa t i en t s w i th progress ive m u s c u l a r dys-

t rophy.

S U M M A R Y

T w o pa t i en t s wi~h o c u l o p h a r y n g e a l m u s c u l a r d vs t ropl ly , in w h o m the p h a r y n x and esophagus were e x a m i n e d at necropsy, are p resen ted . I t is pos tu- la ted tha t the d y s p h a g i a in b o t h r e su l t ed f rom the h is to logic changes of muscu la r d y s t r o p h y which affected the s t r i a t ed m u s c u l a t u r e of the p h a r y n x

and u p p e r esophagus .

R E F E R E N C E S 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.

7. PETERMAX..'~. F.. LIH1NCaOX, G. A., and JA~1els, R. W. Progressive muscular dystrophy with ptosis and dysphagia. Arch Neurol 10:38, 1964.

~. ,~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, l A M A 203.'1003,

1968.

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

Weitzner

12. ROI3E~TS, A. H., and BAMFORrH, J. T h e 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 Olhl tml 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