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Oculopharyngeal Muscular Dystrophy
OCULOPHARYNGEAL MUSCULAR DYSTROPHY CARL CORDES J O H N S O N , M.D.,
AND T O I C H I R O K U W A B A R A ,
Boston,
M.D.
Massachusetts
1
In 1879, Hutchinson described "external ophthalmoplegia" in which blepharoptosis was associated with paralysis of other extraocular muscles. In 1915, Taylor 2 reported on "progressive vagus-glossopharyngeal pa ralysis with ptosis" and stated that the con dition progressed slowly but eventually led to death by starvation. H e studied two gen erations of a French-Canadian family in which it occurred, and the same family was restudied in 1963 by Hayes and associates. 3 T h e latter authors found five cases of oculopharyngeal muscular dystrophy in the third and fourth generations. Collins, 4 in 1922, was the first to posit that most cases of late onset blepharoptosis are due to a primary degeneration of the muscle fibers. Kiloh and Nevin 5 reinforced his thesis. Barbeau, 6 in 1966, described 160 patients of French-Canadian descent with oculopharyngeal muscular dystrophy, living in the province of Quebec. H e traced the fam ily back to a single Frenchman who left the French village of Mortagne in 1634 and migrated to the area near the city of Quebec. T h e two essential characteristics of oculopharyngeal muscular dystrophy are blepharo ptosis and dysphagia. T h e blepharoptosis is invariably bilateral, although the onset in one eyelid may precede slightly the onset in the other. Usually, the onset of dysphagia precedes the onset of blepharoptosis. Like other types of late-onset, hereditary blepharo ptosis, it appears to be a myopathy. It usually occurs in persons of FrenchFrom the Massachusetts Eye and Ear Infirmary (Drs. Johnson and Kuwabara). and the Howe Lab oratory of Ophthalmology (Dr. Kuwabara), Har vard Medical School, Boston, Massachusetts. Reprint requests to Carl Cordes Johnson, M.D., 3 Hawthorne Place, Charles River Park, Boston, MA 02114. 872
Canadian descent, but Victor, Hayes, and Adams, 7 who named the syndrome, studied it in a Russian-Jewish family. O u r series consisted of 131 patients (202 eyes) with acquired blepharoptosis, and of these, 36 patients (72 eyes) were diagnosed as having oculopharyngeal muscular dys trophy. Therefore, 3 3 % of our patients had bilateral blepharoptosis due to oculopharyn geal muscular dystrophy. This high percent age is possibly due to the great number of people of French-Canadian descent living in our geographic area.* In addition to blepharoptosis and dys phagia, two of the patients in this series had weaknesses of the legs, one had weakness of the superior rectus muscles, six had weak ness of the orbicularis muscle, eight had a poor or absent Bell's phenomenon, and two had some limitation of all extraocular muscle movements. I n our patients with oculopharyngeal muscular dystrophy, levator palpebrae su periors ( L P S ) muscle function was about equally divided between those with fair and those with good function, as tested by the usual method. Only one had no function. * In the balance of the cases the diagnoses were as follows: 22 patients (22 eyes), local trauma (in cludes cases secondary to various operative proce dures) ; 46 patients (68 eyes), cause undetermined, but presumably myopathies of undetermined types; two patients (two eyes), third nerve paralysis; two patients (three eyes), myasthenia gravis ; one patient (two eyes), progressive muscular dystrophy; one patient (two eyes), myotonic dystrophy; four pa tients (four eyes), Horner's syndrome; one patient (one eye), postthyroid myopathy; one patient (two eyes), blepharochalasis; three patients (three eyes), secondary to prolonged keratitis; five patients (nine eyes), acquired blepharophimosis; one patient (one eye), multiple sclerosis; two patients (four eyes), senility; one patient (one eye), syphilis; one pa tient (two eyes), external ophthalmoplegia; and two patients (four eves), Kearns-Sayre syndrome.
VOL. 77, NO. 6
OCULOPHARYNGEAL MUSCULAR DYSTROPHY
LPS muscle function is tested by holding a ruler in front of the eyelid. The brow is held so that it cannot be used to elevate the eyelid, and the full excursion of the eyelid from lowest to highest point is then measured off in millimeters on the ruler. An eyelid with no LPS muscle function moves 2 mm or so, due presumably to its attachment to the superior rectus muscle and to relaxation of the orbicularis muscle. Anything more than 3 mm of motion is significant, and 14 or 15 mm is the excursion of the normal eyelid. Blepharoptosis in oculopharyngeal muscu lar dystrophy is a relatively easy type to treat surgically, but overcorrection of most types of acquired blepharoptosis by LPS muscle resection is common. This is in con trast to congenital blepharoptosis where, more often than not, undercorrection is the problem. LPS muscle resections are suitable for all types of acquired blepharoptosis, other than traumatic, and including oculopharyngeal muscular dystrophy, when the excursion of the LPS muscle has been 9 mm or more and fascial slings when the LPS muscle moves 8 mm or less, presuming that these are progressive conditions and that the blepharo-
873
ptosis may worsen, especially in those who have only fair function. One would, of course, expect that if an LPS muscle re section were done, blepharoptosis would recur eventually, but so far no patients who had LPS muscle resection have required reoperation. The results have been good in all but one case of oculopharyngeal muscular dystrophy. In that case we used preserved fascia in stead of autogenous fascia, and the blepharo ptosis recurred on both sides. A reoperation, again with preserved fascia, gave a good result. Preserved fascia was used in one other patient with a good bilateral result. In this patient her own fascia was weak and cobwebby and obviously not strong enough to be used. This is the only time that we have encountered weak and unusable fascia. The L P S muscle resections and fascial slings were done by methods previously de scribed by one of us (C.C.J.), 8 " 10 except for one patient who underwent the FasanellaServat procedure, as modified by Dr. Crowell Beard." Beard's procedure, while theoretically poor because tarsal plate is re sected, produces a good result in patients with congenital or acquired blepharoptosis who
Fig. 1 (Johnson and Kuwabara). Top left, Patient with oculopharyngeal muscular dystrophy preoperatively. He had 10 mm of LPS muscle function bilatei ally. Top right, Primary position after LPS muscle resection. Bottom left, Looking down. Bottom right, 1.ooking up.
874
AMERICAN JOURNAL OF OPHTHALMOLOGY
JUNE, 1974
Fig. 2 (Johnson and Kuwabara). Top left, Patient with oculopharyngeal muscular dystrophy (the brother of the patient shown in Fig. 1). Preoperatively, he had 12 mm of LPS muscle motion in the right eye and 11 mm in the left eye. Top right, Primary position after bilateral LPS muscle resection. Bottom left, Looking down. Bottom right, Looking up. have at least 9 to 10 mm of L P S muscle func tion and not over 2 or 2.5 mm of blepharoptosis. T h e amount of L P S muscle function seems to be more important than the actual amount of blepharoptosis. Incidentally, speci mens taken at operation usually show smooth
and striated muscle fibers, so the FasanellaServat procedure is actually a resection of Miiller's muscle and L P S aponeurosis, and not simply a tar sal resection. Figures 1 through 4 illustrate the surgical results. Specimens for pathologic study were ob-
Fig. 3 (Johnson and Kuwabara). Top left, Patient with oculopharyngeal muscular dystrophy, who had been previously operated. The right eyelid moved 6.5 mm and the left moved 5.5 mm. Top right, Primary position after bilateral autogenous fascia lata frontalis sling. Bottom left, Looking down. Bottom right, Looking up.
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875
Fig. 4 (Johnson and Kuwabara). Top left, Patient with oculopharyngeal muscular dystrophy with no LPS muscle function. Top right, Primary position after a bilateral autogenous fascia lata frontalis sling. Bottom left, Looking down. Bottom right, Looking up.
Fig. 5 (Johnson and Kuwabara). Normal LPS muscle. The muscle cell consists of well-defined myofibrils that are regularly banded. A moderate number of mitochondria are seen in the sarcoplasm and between the myofibrils. Scale rule represents 1 \x (X 14,000).
876
AMERICAN JOURNAL OF OPHTHALMOLOGY
s
\'j.
JUNE, 1974
'{
:w
^i'^gc/x* Fig. 6 (Johnson and Kuwabara). Vacuolar changes in the LPS muscle. Vacuoles in various sizes are seen in the muscle cell. Myofibrils are arranged somewhat irregularly. Mitochondria are electron dense. Scale rule represents 1 n (X43.000). tained at operation by excising a narrow vertical section from the center of the LPS aponeurosis and muscle, starting at the upper border of the tarsus and going up at least 2 cm, so that the material obtained was well into LPS muscle. (Measurements were made in the slightly stretched state, so the tissue the pathologist received was somewhat shorter than this.) The excised tissues were studied electron microscopically after 4% glutaraldehyde fixation. Since the tissue was kept in a moist container for 15 to 30 minutes before fixa tion, the muscle fibers were usually in a re laxed state. The surgically removed tissue in this state was greater than 1 cm in length, and a large number of muscle cells were expected to appear normally (Fig. 5). How ever, connective tissue occupied the studied
areas of the present cases, and histopathologic evaluation was difficult. The most marked change in the examined material was the reduction of the muscle fibers in the excised area of the LPS muscle. A few muscle cells found in the tissue showed pathologic changes in varying de gree. Similar pathologic changes occurred in the orbicularis muscle of these cases. The most common cytologic change was multiple vacuolation in the muscle cell (Fig. 6). Vacuoles were found diffusely in the thin sarcoplasm between fibers. Since small vacuoles were often continuous with both the sarcoplasmic reticulum and T-tube sys tem, dilation of these micro-organelles was possibly the origin of the change. The next most frequent change was dis appearance of Z-bands (Fig. 7). With light
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OCULOPHARYNGEAL MUSCULAR DYSTROPHY
microscopy, these muscle fibers appeared fibrosed. Although both thick and thin fibrils were recognizable, individual muscle fibers were not properly formed within the cell. The number of mitochondria was decreased markedly in these fibrous muscle cells. Some muscle fibers contained advanced degenerative changes (Fig. 8). Light micro scopic study revealed that these muscle fibers were either markedly swollen or strongly chromatophilic, and striations were absent. Also, proliferated nuclei occurred in the abnormal cells. The degenerating muscle cells were extremely electron dense and absent in normal constituents. The dense cell body appeared to be made of condensed and fused myofibrils. Swollen abnormal mito chondria were often found in slightly less degenerated cells. The degenerative cells had
877
abundant electron-dense particles and lipid droplets. Despite the marked disappearance of the LPS muscle cells and the extensive degen erative changes, Miiller's smooth muscle was well preserved (Fig. 9). Except for occasional lipofuscin granules in the cyto plasm, the cytologic appearance of the smooth muscle was normal. In oculopharyngeal muscular dystrophy and in a few related disorders, the pharyngeal musculature cannot propel the bolus of food into the upper esophagus, partly be cause of dysfunction of the pharyngeal mus culature and partly due to the absence of reflex relaxation of the cricopharyngeal mus cle. Evidently degeneration of the pharyn geal musculature results in uncoordinated activity, with material pooling in the pyri-
Fig. 7 (Johnson and Kuwabara). This LPS muscle has lost the striations, including Z-bands. Individual myofibrils are recognizable by thin lines of sarcoplasmic reticulum. The sarcoplasm contains glycogen granules. Mitochondria are missing ( x 80,000).
878
AMERICAN JOURNAL OF OPHTHALMOLOGY
JUNE, 1974
Fig. 8 (Johnson and Kuwabara). The abnormal muscle cell on the right shows dense cytoplasm, vacuoles, and darkened mitochondria. Myofibrils are not recognizable in this cell. A portion of a normal muscle cell is shown on the left. Scale rule represents 1 ji (x25,000). form sinuses and regurgitating into the nasopharynx, and not passing into the normal esophagus. Radiographically the cricopharyngeal muscle does not relax, rather acting as a cork in the bottom of the barrel. Dr. William Montgomery, of the Massa chusetts Eye and E a r Infirmary, has op erated on eight of our patients, using the inferior constrictor myotomy operation. In their reportof 1971, Montgomery and Lynch 1 2 stated that relief of dysphagia in seven pa tients had been maintained from 2J4 to 5 years. These patients were still free of dysphagia at this writing. T h e r e was a par tial failure in one patient, due to multiple deglutitory muscle involvement. SUMMARY
A review of 131 cases of acquired blepharoptosis revealed that 3 3 % were due to
oculopharyngeal muscular dystrophy. Levator palpebrae superioris ( L P S ) muscle re section was the operation of choice when L P S muscle excursion was 9 mm or m o r e ; f ascial slings to the f rontalis were used when L P S muscle excursion was 8 mm or less. T h e results of both procedures were satis factory. T h e dysphagia was treated by cricopharyngeal myotomy with equally satis factory results. Electron microscopy revealed few func tioning striated muscle fibers, indicating that the condition was a primary myopathy. REFERENCES
1. Hutchinson, J.: On ophthalmoplegia externa or symmetrical immobility (partial) of eyes, with ptosis. M. Chir. Tr. London 62:307, 1879. 2. Taylor, E. W.: Progressive vagus-glossopharyngeal paralysis with ptosis. Contribution to group of family diseases. J. Nerv. Ment. Dis. 42: 129, 1915.
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879
Fig. 9 (Johnson and Kuwabara). Miiller's smooth muscle cells found in the vicinity of abnormal L P S muscle. Smooth muscle cell consists of fine myohlaments, numerous dense bodies and mitochondria, and is surrounded by the basement membrane. Scale rule represents 1 \a ( X 13,000).
3. Hayes, R., London, W., Seidman, J., and Embree, L.: Oculopharyngeal muscular dystrophy. N. Engl. J. Med., 268:163, 1963. 4. Collins, E. T . : Hereditary ocular degenerations. Ophthalmic abiotrophies. In International Congress of Ophthalmology: Washington, D.C., April 25-28, 1922, vol. 1. Philadelphia, The Congress, 1922, p. 103. 5. Kiloh, L. G-, and Nevin, S.: Progressive dys trophy of external ocular muscles (ocular myopathy). Brain 74:115, 1951. 6. Barbeau, A . : Symposium iiber progressive Muskeldystrophie. Kuhn, E. (ed.), Berlin, Springer Verlag, 1966, p. 2. 7. Victor, M., Hayes, R., and Adams, R. D.: Oculopharyngeal muscular dystrophy. A familial disease of late life characterized by dysphagia and
progressive ptosis of the eyelids. N. Engl. J. Med. 267:1267, 1962. 8. Johnson, C. C.: Blepharoptosis. A general con sideration of surgical methods, with the results in 162 operations. Am. J. Ophthalmol. 38:129, 1954. 9. : Blepharoptosis. Selection of operation, operative techniques, complications. Arch. Ophthal mol. 66:793, 1961. 10. : Blepharoptosis. Selection of operation, operative techniques, complications. Arch. Ophthal mol. 67:18, 1962. 11. Beard, C.: Ptosis. St. Louis, C. V. Mosby, 1969, p. 136. 12. Montgomery, W. W., and Lynch, J. P . : Oculo pharyngeal muscular dystrophy treated by inferior constrictor mjotomy. Trans. Am. Acad. Ophthalmol. Otolaryngol. 75 :986, 1971.
AND T O I C H I R O K U W A B A R A ,
Boston,
M.D.
Massachusetts
1
In 1879, Hutchinson described "external ophthalmoplegia" in which blepharoptosis was associated with paralysis of other extraocular muscles. In 1915, Taylor 2 reported on "progressive vagus-glossopharyngeal pa ralysis with ptosis" and stated that the con dition progressed slowly but eventually led to death by starvation. H e studied two gen erations of a French-Canadian family in which it occurred, and the same family was restudied in 1963 by Hayes and associates. 3 T h e latter authors found five cases of oculopharyngeal muscular dystrophy in the third and fourth generations. Collins, 4 in 1922, was the first to posit that most cases of late onset blepharoptosis are due to a primary degeneration of the muscle fibers. Kiloh and Nevin 5 reinforced his thesis. Barbeau, 6 in 1966, described 160 patients of French-Canadian descent with oculopharyngeal muscular dystrophy, living in the province of Quebec. H e traced the fam ily back to a single Frenchman who left the French village of Mortagne in 1634 and migrated to the area near the city of Quebec. T h e two essential characteristics of oculopharyngeal muscular dystrophy are blepharo ptosis and dysphagia. T h e blepharoptosis is invariably bilateral, although the onset in one eyelid may precede slightly the onset in the other. Usually, the onset of dysphagia precedes the onset of blepharoptosis. Like other types of late-onset, hereditary blepharo ptosis, it appears to be a myopathy. It usually occurs in persons of FrenchFrom the Massachusetts Eye and Ear Infirmary (Drs. Johnson and Kuwabara). and the Howe Lab oratory of Ophthalmology (Dr. Kuwabara), Har vard Medical School, Boston, Massachusetts. Reprint requests to Carl Cordes Johnson, M.D., 3 Hawthorne Place, Charles River Park, Boston, MA 02114. 872
Canadian descent, but Victor, Hayes, and Adams, 7 who named the syndrome, studied it in a Russian-Jewish family. O u r series consisted of 131 patients (202 eyes) with acquired blepharoptosis, and of these, 36 patients (72 eyes) were diagnosed as having oculopharyngeal muscular dys trophy. Therefore, 3 3 % of our patients had bilateral blepharoptosis due to oculopharyn geal muscular dystrophy. This high percent age is possibly due to the great number of people of French-Canadian descent living in our geographic area.* In addition to blepharoptosis and dys phagia, two of the patients in this series had weaknesses of the legs, one had weakness of the superior rectus muscles, six had weak ness of the orbicularis muscle, eight had a poor or absent Bell's phenomenon, and two had some limitation of all extraocular muscle movements. I n our patients with oculopharyngeal muscular dystrophy, levator palpebrae su periors ( L P S ) muscle function was about equally divided between those with fair and those with good function, as tested by the usual method. Only one had no function. * In the balance of the cases the diagnoses were as follows: 22 patients (22 eyes), local trauma (in cludes cases secondary to various operative proce dures) ; 46 patients (68 eyes), cause undetermined, but presumably myopathies of undetermined types; two patients (two eyes), third nerve paralysis; two patients (three eyes), myasthenia gravis ; one patient (two eyes), progressive muscular dystrophy; one patient (two eyes), myotonic dystrophy; four pa tients (four eyes), Horner's syndrome; one patient (one eye), postthyroid myopathy; one patient (two eyes), blepharochalasis; three patients (three eyes), secondary to prolonged keratitis; five patients (nine eyes), acquired blepharophimosis; one patient (one eye), multiple sclerosis; two patients (four eyes), senility; one patient (one eye), syphilis; one pa tient (two eyes), external ophthalmoplegia; and two patients (four eves), Kearns-Sayre syndrome.
VOL. 77, NO. 6
OCULOPHARYNGEAL MUSCULAR DYSTROPHY
LPS muscle function is tested by holding a ruler in front of the eyelid. The brow is held so that it cannot be used to elevate the eyelid, and the full excursion of the eyelid from lowest to highest point is then measured off in millimeters on the ruler. An eyelid with no LPS muscle function moves 2 mm or so, due presumably to its attachment to the superior rectus muscle and to relaxation of the orbicularis muscle. Anything more than 3 mm of motion is significant, and 14 or 15 mm is the excursion of the normal eyelid. Blepharoptosis in oculopharyngeal muscu lar dystrophy is a relatively easy type to treat surgically, but overcorrection of most types of acquired blepharoptosis by LPS muscle resection is common. This is in con trast to congenital blepharoptosis where, more often than not, undercorrection is the problem. LPS muscle resections are suitable for all types of acquired blepharoptosis, other than traumatic, and including oculopharyngeal muscular dystrophy, when the excursion of the LPS muscle has been 9 mm or more and fascial slings when the LPS muscle moves 8 mm or less, presuming that these are progressive conditions and that the blepharo-
873
ptosis may worsen, especially in those who have only fair function. One would, of course, expect that if an LPS muscle re section were done, blepharoptosis would recur eventually, but so far no patients who had LPS muscle resection have required reoperation. The results have been good in all but one case of oculopharyngeal muscular dystrophy. In that case we used preserved fascia in stead of autogenous fascia, and the blepharo ptosis recurred on both sides. A reoperation, again with preserved fascia, gave a good result. Preserved fascia was used in one other patient with a good bilateral result. In this patient her own fascia was weak and cobwebby and obviously not strong enough to be used. This is the only time that we have encountered weak and unusable fascia. The L P S muscle resections and fascial slings were done by methods previously de scribed by one of us (C.C.J.), 8 " 10 except for one patient who underwent the FasanellaServat procedure, as modified by Dr. Crowell Beard." Beard's procedure, while theoretically poor because tarsal plate is re sected, produces a good result in patients with congenital or acquired blepharoptosis who
Fig. 1 (Johnson and Kuwabara). Top left, Patient with oculopharyngeal muscular dystrophy preoperatively. He had 10 mm of LPS muscle function bilatei ally. Top right, Primary position after LPS muscle resection. Bottom left, Looking down. Bottom right, 1.ooking up.
874
AMERICAN JOURNAL OF OPHTHALMOLOGY
JUNE, 1974
Fig. 2 (Johnson and Kuwabara). Top left, Patient with oculopharyngeal muscular dystrophy (the brother of the patient shown in Fig. 1). Preoperatively, he had 12 mm of LPS muscle motion in the right eye and 11 mm in the left eye. Top right, Primary position after bilateral LPS muscle resection. Bottom left, Looking down. Bottom right, Looking up. have at least 9 to 10 mm of L P S muscle func tion and not over 2 or 2.5 mm of blepharoptosis. T h e amount of L P S muscle function seems to be more important than the actual amount of blepharoptosis. Incidentally, speci mens taken at operation usually show smooth
and striated muscle fibers, so the FasanellaServat procedure is actually a resection of Miiller's muscle and L P S aponeurosis, and not simply a tar sal resection. Figures 1 through 4 illustrate the surgical results. Specimens for pathologic study were ob-
Fig. 3 (Johnson and Kuwabara). Top left, Patient with oculopharyngeal muscular dystrophy, who had been previously operated. The right eyelid moved 6.5 mm and the left moved 5.5 mm. Top right, Primary position after bilateral autogenous fascia lata frontalis sling. Bottom left, Looking down. Bottom right, Looking up.
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OCULOPHARYNGEAL MUSCULAR DYSTROPHY
875
Fig. 4 (Johnson and Kuwabara). Top left, Patient with oculopharyngeal muscular dystrophy with no LPS muscle function. Top right, Primary position after a bilateral autogenous fascia lata frontalis sling. Bottom left, Looking down. Bottom right, Looking up.
Fig. 5 (Johnson and Kuwabara). Normal LPS muscle. The muscle cell consists of well-defined myofibrils that are regularly banded. A moderate number of mitochondria are seen in the sarcoplasm and between the myofibrils. Scale rule represents 1 \x (X 14,000).
876
AMERICAN JOURNAL OF OPHTHALMOLOGY
s
\'j.
JUNE, 1974
'{
:w
^i'^gc/x* Fig. 6 (Johnson and Kuwabara). Vacuolar changes in the LPS muscle. Vacuoles in various sizes are seen in the muscle cell. Myofibrils are arranged somewhat irregularly. Mitochondria are electron dense. Scale rule represents 1 n (X43.000). tained at operation by excising a narrow vertical section from the center of the LPS aponeurosis and muscle, starting at the upper border of the tarsus and going up at least 2 cm, so that the material obtained was well into LPS muscle. (Measurements were made in the slightly stretched state, so the tissue the pathologist received was somewhat shorter than this.) The excised tissues were studied electron microscopically after 4% glutaraldehyde fixation. Since the tissue was kept in a moist container for 15 to 30 minutes before fixa tion, the muscle fibers were usually in a re laxed state. The surgically removed tissue in this state was greater than 1 cm in length, and a large number of muscle cells were expected to appear normally (Fig. 5). How ever, connective tissue occupied the studied
areas of the present cases, and histopathologic evaluation was difficult. The most marked change in the examined material was the reduction of the muscle fibers in the excised area of the LPS muscle. A few muscle cells found in the tissue showed pathologic changes in varying de gree. Similar pathologic changes occurred in the orbicularis muscle of these cases. The most common cytologic change was multiple vacuolation in the muscle cell (Fig. 6). Vacuoles were found diffusely in the thin sarcoplasm between fibers. Since small vacuoles were often continuous with both the sarcoplasmic reticulum and T-tube sys tem, dilation of these micro-organelles was possibly the origin of the change. The next most frequent change was dis appearance of Z-bands (Fig. 7). With light
VOL. 77, NO. 6
OCULOPHARYNGEAL MUSCULAR DYSTROPHY
microscopy, these muscle fibers appeared fibrosed. Although both thick and thin fibrils were recognizable, individual muscle fibers were not properly formed within the cell. The number of mitochondria was decreased markedly in these fibrous muscle cells. Some muscle fibers contained advanced degenerative changes (Fig. 8). Light micro scopic study revealed that these muscle fibers were either markedly swollen or strongly chromatophilic, and striations were absent. Also, proliferated nuclei occurred in the abnormal cells. The degenerating muscle cells were extremely electron dense and absent in normal constituents. The dense cell body appeared to be made of condensed and fused myofibrils. Swollen abnormal mito chondria were often found in slightly less degenerated cells. The degenerative cells had
877
abundant electron-dense particles and lipid droplets. Despite the marked disappearance of the LPS muscle cells and the extensive degen erative changes, Miiller's smooth muscle was well preserved (Fig. 9). Except for occasional lipofuscin granules in the cyto plasm, the cytologic appearance of the smooth muscle was normal. In oculopharyngeal muscular dystrophy and in a few related disorders, the pharyngeal musculature cannot propel the bolus of food into the upper esophagus, partly be cause of dysfunction of the pharyngeal mus culature and partly due to the absence of reflex relaxation of the cricopharyngeal mus cle. Evidently degeneration of the pharyn geal musculature results in uncoordinated activity, with material pooling in the pyri-
Fig. 7 (Johnson and Kuwabara). This LPS muscle has lost the striations, including Z-bands. Individual myofibrils are recognizable by thin lines of sarcoplasmic reticulum. The sarcoplasm contains glycogen granules. Mitochondria are missing ( x 80,000).
878
AMERICAN JOURNAL OF OPHTHALMOLOGY
JUNE, 1974
Fig. 8 (Johnson and Kuwabara). The abnormal muscle cell on the right shows dense cytoplasm, vacuoles, and darkened mitochondria. Myofibrils are not recognizable in this cell. A portion of a normal muscle cell is shown on the left. Scale rule represents 1 ji (x25,000). form sinuses and regurgitating into the nasopharynx, and not passing into the normal esophagus. Radiographically the cricopharyngeal muscle does not relax, rather acting as a cork in the bottom of the barrel. Dr. William Montgomery, of the Massa chusetts Eye and E a r Infirmary, has op erated on eight of our patients, using the inferior constrictor myotomy operation. In their reportof 1971, Montgomery and Lynch 1 2 stated that relief of dysphagia in seven pa tients had been maintained from 2J4 to 5 years. These patients were still free of dysphagia at this writing. T h e r e was a par tial failure in one patient, due to multiple deglutitory muscle involvement. SUMMARY
A review of 131 cases of acquired blepharoptosis revealed that 3 3 % were due to
oculopharyngeal muscular dystrophy. Levator palpebrae superioris ( L P S ) muscle re section was the operation of choice when L P S muscle excursion was 9 mm or m o r e ; f ascial slings to the f rontalis were used when L P S muscle excursion was 8 mm or less. T h e results of both procedures were satis factory. T h e dysphagia was treated by cricopharyngeal myotomy with equally satis factory results. Electron microscopy revealed few func tioning striated muscle fibers, indicating that the condition was a primary myopathy. REFERENCES
1. Hutchinson, J.: On ophthalmoplegia externa or symmetrical immobility (partial) of eyes, with ptosis. M. Chir. Tr. London 62:307, 1879. 2. Taylor, E. W.: Progressive vagus-glossopharyngeal paralysis with ptosis. Contribution to group of family diseases. J. Nerv. Ment. Dis. 42: 129, 1915.
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879
Fig. 9 (Johnson and Kuwabara). Miiller's smooth muscle cells found in the vicinity of abnormal L P S muscle. Smooth muscle cell consists of fine myohlaments, numerous dense bodies and mitochondria, and is surrounded by the basement membrane. Scale rule represents 1 \a ( X 13,000).
3. Hayes, R., London, W., Seidman, J., and Embree, L.: Oculopharyngeal muscular dystrophy. N. Engl. J. Med., 268:163, 1963. 4. Collins, E. T . : Hereditary ocular degenerations. Ophthalmic abiotrophies. In International Congress of Ophthalmology: Washington, D.C., April 25-28, 1922, vol. 1. Philadelphia, The Congress, 1922, p. 103. 5. Kiloh, L. G-, and Nevin, S.: Progressive dys trophy of external ocular muscles (ocular myopathy). Brain 74:115, 1951. 6. Barbeau, A . : Symposium iiber progressive Muskeldystrophie. Kuhn, E. (ed.), Berlin, Springer Verlag, 1966, p. 2. 7. Victor, M., Hayes, R., and Adams, R. D.: Oculopharyngeal muscular dystrophy. A familial disease of late life characterized by dysphagia and
progressive ptosis of the eyelids. N. Engl. J. Med. 267:1267, 1962. 8. Johnson, C. C.: Blepharoptosis. A general con sideration of surgical methods, with the results in 162 operations. Am. J. Ophthalmol. 38:129, 1954. 9. : Blepharoptosis. Selection of operation, operative techniques, complications. Arch. Ophthal mol. 66:793, 1961. 10. : Blepharoptosis. Selection of operation, operative techniques, complications. Arch. Ophthal mol. 67:18, 1962. 11. Beard, C.: Ptosis. St. Louis, C. V. Mosby, 1969, p. 136. 12. Montgomery, W. W., and Lynch, J. P . : Oculo pharyngeal muscular dystrophy treated by inferior constrictor mjotomy. Trans. Am. Acad. Ophthalmol. Otolaryngol. 75 :986, 1971.