NOTES AND NEW DEVELOPMENTS
INFLAMMATORY MYOPATHY IN OCULOPHARYNGEAL DYSTROPHY E. Peter Bosch, MD. James D. C. Gowans, MD, and Theodore Munsat, MD
Abstract: A 75-year-old French-Canadianwoman with fa-
milial oculopharyngeal dystrophy demonstrated histopathologic alterations similar to those of idiopathic polymyositis. A second biopsy obtained 15 months later was more consistent with previously reported cases. It is suggested that certain patients with oculopharyngeal dystrophy may pass through an initial phase of secondary muscle inflammation similar to that seen in some other heritable myopathies. MUSCLE EL NERVE
2~73-77
1979
Oculopharyngeal dystrophy is a rare form of progressive ophthalmoplegia with onset late in life, dysphagia, and autosonial dominant inheritance. It is frequently found in French-Canadian families, in whom the disorder has been traced back to a common French ancestor who landed in Q u c k c in the 17th century.2 Other ethnic groups are rarely a f f e c ~ e d . ~ * "Progressive *~~ ptosis and dysphagia charactcristically begin after the fourth decade, As the disease slowly worsens, most affected individuals develop ophthalmoparesis, facial weakness, and proximal limb ~ e a k n e s s . ~ *In~ ~contrast * * ~ to other forms of progressive ophthalmoplegia, ptosis without extraocular muscle. involvement is frequently en~ountered.'.~.'~ T h e dysphagia may become severe with increasing age and is reportedly alleviated by cricopharyngeal myotomy .I2 I iistolathologic report^^^^'^'^**^^^^ show nonspecific myjpathic alterations in cranial, extracranial, and h r y n g e a l striated muscles. T h e few available au3psy s t ~ d i e s 'confirm ~ , ~ ~ that thc disorder is a dys-
Myositis in Oculopharyngeal Dystrophy
trophic process and is not due to degeneration of motor neurons. Few biopsies have been studied with histochemistry. In a series of patients of Spanish-American descent, Dubowitz and Brooke6 found variation in fiber size, occasional internal nuclei, small angulated fibers, and prominent changes in fiber architecture. Randomly distributed single fibers contained "rimmed vacuoles'' (that is, punched-out lesions lined by a granular hematoxylinophilic layer), and many showed a moth-eaten and whorled appearance of the intermyofibrillar network with oxidative enzyme reactions. One electron-microscopic study of a limb musclelo demonstrated abnormalities of mitochondria and fingerprint inclusions, while two o t h e r P R showed nonspecific degerierative changes without mitochondria1 alterations. No studies have reported inflammatory changes in the muscle. We describe a patient with faniilial oculopharyngeal dystrophy in whom initial biopsy revealed an inflammatory myopathy consistent with polymyositis. Although the histopathologic picture was impossible to distinguish from that of idiopathic polymyosit.is, the clinical picture was not consistent with the latter diagnosis. This supports the concept that certain patients with oculopha-
From Ihe Neurcmuscular Unit and the Department of Neurology (Drs. Bosch and Munsat) and the Deparfmcnt of Internal Medicine (Dr. Go. wans), Tufts-New England Medical Center Hospital. Boston. MA. Acknowledgment: This investigation was supporled in part by grants from the Muscular Dystrophy Association of America. Address roprint requests to Dr. Munsat at (he Department ol Neurology, Tults-Ncw England Medical Center Hospital. 171 Harrison Ave., Boston, MA02111. Submitted for publication June 28. 1978; accepted for puhlication October 5. 1978. oi4aa9x/o2oi/oo73 soo.oo 1979 Houghton Mifllin Prolessional Publishers
MUSCLE & NERVE
JanlFeb 1979
73
ryngeal dystrophy may pass through a secondary polymyositic stage, as has been described in other dystrophies. CASE REPORT
A 75-year-old woman of French-Canadian descent presented with progressive ptosis, dysphagia, and proximal limb weakness. At age 68 she had noted progressive difficulty in swallowing solid food. Soon thereafter, she became aware of ptosis. T h e dysphagia gradually worsened, resulting in a 70-lb weight loss over a seven-year period. Her meals were interrupted by frequent coughing spelIs, and occasionally she suffered nasal regurgitation of fluids. Two years later, at age 70, she developed hip weakness and had difficulty climbing stairs and rising from a chair. T h e patient was admitted to another hospital in April 1976. Her serum creatine kinase (CK) was motlerately elevated to 1.580 1U (normal: 0-120 IU). .4 qitadriceps muscle biopsy revealed an acute inflammatory myopathy. O n the basis of the biopsy findings, which were felt to be consistent with polyrnyositis, daily high-dose prednisone therapy was started. This resulted in nornialization of serum CK levels hui no clinical improvement. A brief trial of pyridostigtnine was also unsuccessful. While on 30 mg prednisone daily-,the patient noted increasing hip and thigh weakness. In May 1977, she fell antl suffered a fracture of the pel\.is. After the fall, she could walk only with assistance. A t age 65, the patient's French-Canadian father had developed late-onset ptosis, dysphagia, antl hip weakness, and had asphyxiated during a meal. Two paternal uncles had also developed late-onset ptosis, and one paternal cousin with ptosis h a d had a levator palpebrae supcrioris resection at age 54. T h e patient's only daughter was not affecled when she was examined at age 46. As a result of the deterioration, the patient was referred to 'I'ufts-New England Medical Center for reevaluation. On examination, she appeared emaciated; her weight was 45 kg arid her height 160 cm. There was symmetrical partial ptosis. Her forehead was consrandy wrinkled, and her evebrows were elevated aboie the supraorbital ridges (fig. I ). Extraocular movements were full except for rnild impairment of up-gaze. The pupils were equal and reacted t o light as well as to acco~~iniodation. 'There was symmetrical weakness of the facial muscles. The pharyngeal reflex was present. Swallowing of solids and liquids was slow arid was iriterruptcd by coughing. T h e neck was thin, and neck flexors and st.ernocleidomastoid muscles were weak. Shoulder girdle, arms, and thighs were diffusely wasted. There was moderate symmetrical weakness (Grade 4 b y Medical Research Council criteria) of deltoids, supraspinati arid infrabpiriati, biceps, triceps, hip flexors, extensors, abductors, quadriceps, and hamstring muscles. Strength in distal muscle groups was preserved. Percussion and action myotonia was absent. T h e tendon reflexes of the legs were hypoactive. T h e patient's gait was cautious, heavy-footed, and waddling. An intraverious injection of
74
Myositis in Oculopharyngeal Dystrophy
10 mg of edrophonium chloride had no effect. Laboratory investigations showed normal levels of serum CK and aldolase. Contrast cineradiography of the esophagus demonstrated pooling of barium in the pyi-iforni sinus and irregular relaxation of the cricopharyngeus muscle. Tracheal aspiration of barium was noted with each attempt to swallow. Motor conduction velocity of the median nerve was normal (51 rnisec). Electromyographic stiidies of several proximal arm and leg rnuscles revealed normal resting activity and abundant brief, low-amplitude arid polyphasic motor unit potentials with early and full recruitment. Repetitive, supramaximal, three-per-second facial nerve stimulation failed to demonstrate a decrement of the orbicularis oculi muscle. A second muscle biopsy was obtaincd. MUSCLE BIOPSY FINDINGS
Paraffin-embedded, hematoxylin and eosin (H&E)and trichrome-stained sections of the initial quadriceps muscle biopsy demonstrated marked inflammatory alterations similar to those of polymyositis. Widespread fiber necrosis and phagocytosis were present, as were small, basophilic regenerating fibers with vesicular nuclei, occasional internal nuclei, and moderate variation in fiber size. Striking interstitial and rare perivascular infiltration with lymphocytes and histiocytes was present (fig. 2). Perifascicular atrophy and eridomysial fibrosis were not seen. After 15 months of treatment with prednisone, a second biopsy from the left deltoid muscle was obtained. Cryostat sections were processed by routine methods for light microscopy and histochemistry.6 Histogram, atrophy, and hypertrophy factors of type 1 and type 2 were calculated according to the method of Dubowitz and Brooke.6 The previously observed inflammatory changes were no longer evident. There were frequent small, angulated fibers that stained dark with the NADH-TR reaction, as well as occasional internal nuclei, rare degenerating and regenerating fibers, and prominent moth-eaten or whorled fibers. On H8cE stain, some fibers were seen to contain central or subsarcolernnial vacuoles surrounded by a basophilic rim. Both fiber types were involved. The histogram confirmed the visual impression of mild type 2 fiber atrophy (fig. 3). The findings of the second hiopsy were more consistent with the clinical picture of' oculopharyngeal dystrophy and possible superimposed corticosteroid myopathy. Prednisone was gradually tapered and discontinued. Two months later, the patient noted some functional improvement ir, walking, and her serum CK levels remainec normal.
MUSCLE & NERVE
Jan/Feb 1979
Figure 1 . Symrnetncal ptos/s with compensatory contracbon of frontahs muscle
hgure 2 ln/t/alquadnceps muscle b/opsy shows extenwe mtershtiai mf/mmatorytnfkation Paraffin section, hematoxylin & eosin Bar = I00
DISCUSSION
In some cases, the distinction between pol ym yositis and muscular dystrophy can be difficult to establish. In their critical review of' inflammatory myopathics, Bohan and Peter4 proposed four criteria, excluding the rash in dermatomyositis, by which polymyositis could be defined. Three of these criteria-weakness of limb-girdle muscles, elevation of serum CK, and muscle biopsy evidence of necrosis, regeneration, and in flammation-were initially met by our patient, although the distribution of weakness was atypical. Dysphagia is common, but the eye muscles are almost always spared in
Myositis in Oculopharyngeal Dystrophy
polymyositis or dermatomyositis. '4 case in which ophthalmoplegia was seen in dermatomyositi~'~ could have represented a patient with myasthenia gravis. Inlerstitial infhmmation and fiber necrosis indistinguishable from polymyositis are seen in almost 25% of muscle biopsies from rnyasthenic patient.~.~," 'This alternate diagnosis was rejected in our patient, since there was no fluctuation in weakness, no response to cholinergic drugs, and no decremental response to repetitive nerve stimulation. The family history and stereotyped clinical manifestations of our case were highly typical of oculopharyngeal dystrophy.
MUSCLE & NERVE
JanlFeb 1979
75
Fiber Type
1
2
Percentage 44 Mean Diometer ( g n l 6 2
56 42
SD AF HF
13
18
D 409
259 (43
-Y LL
0
lx 20-
m w
fz 10
-
L
0-9 10-
I
FIBER DIAMETER ( p m )
Figure 3 (A) Second deltoid muscle biopsy shows small angulated fibers and internal displacement of nuclei in large fibers A subsarcolemmal vacuole lined by a granular basophilic rim 1s seen in one anguiated fiber Cryostat sectfon, hematoxylin & eosin Bar = 50 g?i (8) Dark, angulated, and moth-eaten fibers Cryostat section, NADH-TR Bar = 50 g?i (C) Histogram shows increased variation fn hber size and type 2 fiber atrophy Hypertrophy factors (HF) for type 1 and atrophy factors (AF) for type 2 fibers are elevated
76
Myositis in Oculopharyngeal Dystrophy
We cannot exclude 1.he possibility that an independent, acquired polymyositis was superimposed on the genetic disorder, but this seems unlikely in light of the reported polym yositic reactions in other heritable muscular dystrophies.I6 In their series of progressive ophthalmoplegia, Rosenberg et all9 reported a similar patient with familial ptosis and ophthalmoplegia who developed limb-girdle weakness late in life, and whose biopsy showed evidence of polymyositis. Inflammatory cell in filtrations are not uncommon in muscular dystrophies. They have been reported in 36% of muscle biopsies from patients with various dystrophies, including Ihchenne muscular dystrophy,8 and in 50%'of patients with facioscapulohurneral dystrophy.'j .4n inflammatory Inyopathy of facioscapulohumeral distribution has been observed repeatedly.3~'4~'6.2u Some of these patients had dominantly inherited facioscapulohumeral dystrophy, while in others there was no family history of similar disease. Because of histopathologic similarities to idiopathic polymyositis, several of these patients were treated with prednisone. In a recent report,I3 six patients treated with prednisorie for periods ranging up to five years derived no long-term therapeutic benefit from it, although serum CK values were consistently lowered. The experience of our patient was similar. T h e inflammatory response in dystrophies has been related to a secondary immune response triggered by underlying muscle degeneration." Why an inflammatory response is present in some but not all cases of dystrophy is not yet known. The presence of inflammation both in idiopathic polyrnyositis and in miiscular dystrophy can create diagnostic problems. Histopathologically, hypertrophy of fibers favors a dystrophic myopathy:6 while extensive vacuolar liber degeneration and regeneration are more commonly encountered in polymyositis.* On the other hand, inorphologic criteria may overlap. In these situations, certain negative criteria'' (such as no family history of similar disease) may point toward a diagnosis of pol ymyositis. A positive family history of similar disease, as was seen in our patient, supports a diagnosis of secondary inflammation in an inherited disease; such a family history may also predict an unfavorable response to immunosuppressive therapy.
MUSCLE & NERVE
JaniFeb 1979
REFERENCES inyopathy with facioscapulohurrirrdl distribution. lVeUT(Jl(JgJ (Minneap) 22:335-347, 1972. 15. Murphy SF, Dracliman DB: The oculopharyrigeal syndrome. 1 h M A 203: 1003- 1008, 1968. 16. Papapetropoulos T A , Bradley WG: T h e role of secondary polymyositis in the muscular dystrophy syndromes. Proceeditigs of the Third Infernatiottnl Congress on Muscle Di.seusrs. Amsterdam. Excerpta Mcdica, 1974, p 91. 17. Pcterman AF, Lillington Grl, Jamplis RW: Progressive 108, 1973. muscular dystrophy with ptosis and dysphagia. Arch Neurol Bohan .4, Peter JB: Polymyositis and dermatomyositis, part 10:52-58, 1964. 1. N E n g l J Med 292:344-347, 1975. Bray GM, K a a r w n M , Ross R T : Ocular myopathica with 18. Rebeiz JJ, Caulfield JB, Adams RD: Ocnlopharyngeal dystrophy-A prrsenescent myopathy. A clinicu-pathologic dysphagid. l\ieurologj (hiirineap) 15:678-684, 1965. study. I n Brunette JR. Bar-beau A (Editors): Proreedings U J Dubowitz V, Brooke MH: Mutcle Biopsy: .4 M o d e m Approuch. the Second Congress on ,Vrurogmr/ict cind ,\:ell roophthalttiolog~. London, WB Saunders. 1973. Amsterdam, Excerpta Sledica, 1969, pp 12-3 1. Fenichel GM: Muscle lesions in myasthenia gravis. A n n JVY 19. Rosenberg RN, Schotland DL, Lmelace RE, Rowland LP: Arad Sri 135:60-78, 1966. Progressive ophthalrrioplegia: report of cases. Arch S e u r o l Jerusalem T : Die bioptisclie-histologische Differentialdi19:362-376, 1968. agnose der Polyrnyositis und d e r progressiven Muskeldys20. Rothstein TL, Carlsori CB, Sumi Sh4: Polymyositis with fatrophie. Dttrh Z iVmwnAezlk 191:125-141, 1967. cioscapulohuinei-al distriburion. Arrh Seurol 2533 13-3 19, Johnson CC, Kuwabara T : Oculopharyngeal muscular dys1971. trophy-. Am,J Ophthnlmol 71:872-879, 1974. 21. Rowland LP, Clark C, Olarte M : Therapy for dermatoJulien J , Vital C, Vallat JM, \:allat hi, LeBlanc M: Oculomyositis and polymyositis. In Griggs RC, Moxley R T (Edpharyngeal muscular dystrophy. A case with abnornial in N P U ~ ( J ~Vol ~ ~ ;17. , New York, Raven itors): ,4rlilnnc~.~ mitochondria and “fingerprint” inclusions. 1 ,Veurol Sri Press, 1977, p p 63-97. 2 1:165-169, 1974. 22. Rowland LP, Hoefcr PF.4, Aranow H : Myasthenic synLewis I: Oculopharyngeal muscular dystrophy. 4 family dromcs. RPSPubZAssoc Res N e r 7 ~M e r i t Dis 38:548-600, 1960. study. In Brunette JR, Barbeau .4 (Editor): Proweding> .f the Second Congrrss o n ,Veurogrnetics and ,2’eiLroo~~~thalmolo,~. 23. Susac JO, Garcia-Mullin R, Glaser JS: Ophthalmoplegia in dermatomyositis. SeuroZogy (Minneap) 23:305-310, 1973. Amsterdam, Excerpta Medica, 1969, pp 4-1 1. 24. Victor M, Hayes K, Adams RI): Oculopharyngeal dystroMontgomery WW, Lynch JP: Oculopharyngeal muscular phy. .4 familial disease of late life characterized by dysdystrophy treated by inferior constrictor myotoniy. Trans phagia and progressive ptosis of the eyelids. ,\‘ Engl J M p d A m 4cnd Ophthnlmol Otolmyrigul 75:986-993, 1971. 267:1267-1252, 1962. Munsat T L , Bradley WG: Serum creatine phosphokinase 25. Weitzner S: Changes in the pharyngeal and esophageal levels and prednisone-treated muscle weakness. Neurology musculature in oculopharyngeal muscular dystrophy. Re(Minneap) 27:96-97, 1977. Munsat ‘I L, Piper 11, Canrilla P, Mednick .I: Inflammatory port of two cases. A m J Dzg Dzs 14:805-810, 1969.
1. Amyot K : Hereditary, faniilial and acquired ptosis of l a ~ e onset. Can .Wed A.\socJ 59:434-438, 1948. 2. Barbeau .4: T h e syndrome of hereditary late-onset ptosis arid dysphagia in French Canada. In Kulin E (Editor): Pro.11utculur Oytrophy: .Wyotonra, AVlyo.tthmia. Berlin, er-Verlag, 1966, pp 102-109. 3. Bates D, Stevens JC, Hudgson P: Polyrnvositis with involvement of facial and distal musculature.,] N m r d Sci 19:105-
4. 5.
6. 7. 8. 9. 10.
1 1.
12. 13.
14.
Myositis in Oculopharyngeal Dystrophy
MUSCLE & NERVE
JaniFeb 1979
77
INFLAMMATORY MYOPATHY IN OCULOPHARYNGEAL DYSTROPHY E. Peter Bosch, MD. James D. C. Gowans, MD, and Theodore Munsat, MD
Abstract: A 75-year-old French-Canadianwoman with fa-
milial oculopharyngeal dystrophy demonstrated histopathologic alterations similar to those of idiopathic polymyositis. A second biopsy obtained 15 months later was more consistent with previously reported cases. It is suggested that certain patients with oculopharyngeal dystrophy may pass through an initial phase of secondary muscle inflammation similar to that seen in some other heritable myopathies. MUSCLE EL NERVE
2~73-77
1979
Oculopharyngeal dystrophy is a rare form of progressive ophthalmoplegia with onset late in life, dysphagia, and autosonial dominant inheritance. It is frequently found in French-Canadian families, in whom the disorder has been traced back to a common French ancestor who landed in Q u c k c in the 17th century.2 Other ethnic groups are rarely a f f e c ~ e d . ~ * "Progressive *~~ ptosis and dysphagia charactcristically begin after the fourth decade, As the disease slowly worsens, most affected individuals develop ophthalmoparesis, facial weakness, and proximal limb ~ e a k n e s s . ~ *In~ ~contrast * * ~ to other forms of progressive ophthalmoplegia, ptosis without extraocular muscle. involvement is frequently en~ountered.'.~.'~ T h e dysphagia may become severe with increasing age and is reportedly alleviated by cricopharyngeal myotomy .I2 I iistolathologic report^^^^'^'^**^^^^ show nonspecific myjpathic alterations in cranial, extracranial, and h r y n g e a l striated muscles. T h e few available au3psy s t ~ d i e s 'confirm ~ , ~ ~ that thc disorder is a dys-
Myositis in Oculopharyngeal Dystrophy
trophic process and is not due to degeneration of motor neurons. Few biopsies have been studied with histochemistry. In a series of patients of Spanish-American descent, Dubowitz and Brooke6 found variation in fiber size, occasional internal nuclei, small angulated fibers, and prominent changes in fiber architecture. Randomly distributed single fibers contained "rimmed vacuoles'' (that is, punched-out lesions lined by a granular hematoxylinophilic layer), and many showed a moth-eaten and whorled appearance of the intermyofibrillar network with oxidative enzyme reactions. One electron-microscopic study of a limb musclelo demonstrated abnormalities of mitochondria and fingerprint inclusions, while two o t h e r P R showed nonspecific degerierative changes without mitochondria1 alterations. No studies have reported inflammatory changes in the muscle. We describe a patient with faniilial oculopharyngeal dystrophy in whom initial biopsy revealed an inflammatory myopathy consistent with polymyositis. Although the histopathologic picture was impossible to distinguish from that of idiopathic polymyosit.is, the clinical picture was not consistent with the latter diagnosis. This supports the concept that certain patients with oculopha-
From Ihe Neurcmuscular Unit and the Department of Neurology (Drs. Bosch and Munsat) and the Deparfmcnt of Internal Medicine (Dr. Go. wans), Tufts-New England Medical Center Hospital. Boston. MA. Acknowledgment: This investigation was supporled in part by grants from the Muscular Dystrophy Association of America. Address roprint requests to Dr. Munsat at (he Department ol Neurology, Tults-Ncw England Medical Center Hospital. 171 Harrison Ave., Boston, MA02111. Submitted for publication June 28. 1978; accepted for puhlication October 5. 1978. oi4aa9x/o2oi/oo73 soo.oo 1979 Houghton Mifllin Prolessional Publishers
MUSCLE & NERVE
JanlFeb 1979
73
ryngeal dystrophy may pass through a secondary polymyositic stage, as has been described in other dystrophies. CASE REPORT
A 75-year-old woman of French-Canadian descent presented with progressive ptosis, dysphagia, and proximal limb weakness. At age 68 she had noted progressive difficulty in swallowing solid food. Soon thereafter, she became aware of ptosis. T h e dysphagia gradually worsened, resulting in a 70-lb weight loss over a seven-year period. Her meals were interrupted by frequent coughing spelIs, and occasionally she suffered nasal regurgitation of fluids. Two years later, at age 70, she developed hip weakness and had difficulty climbing stairs and rising from a chair. T h e patient was admitted to another hospital in April 1976. Her serum creatine kinase (CK) was motlerately elevated to 1.580 1U (normal: 0-120 IU). .4 qitadriceps muscle biopsy revealed an acute inflammatory myopathy. O n the basis of the biopsy findings, which were felt to be consistent with polyrnyositis, daily high-dose prednisone therapy was started. This resulted in nornialization of serum CK levels hui no clinical improvement. A brief trial of pyridostigtnine was also unsuccessful. While on 30 mg prednisone daily-,the patient noted increasing hip and thigh weakness. In May 1977, she fell antl suffered a fracture of the pel\.is. After the fall, she could walk only with assistance. A t age 65, the patient's French-Canadian father had developed late-onset ptosis, dysphagia, antl hip weakness, and had asphyxiated during a meal. Two paternal uncles had also developed late-onset ptosis, and one paternal cousin with ptosis h a d had a levator palpebrae supcrioris resection at age 54. T h e patient's only daughter was not affecled when she was examined at age 46. As a result of the deterioration, the patient was referred to 'I'ufts-New England Medical Center for reevaluation. On examination, she appeared emaciated; her weight was 45 kg arid her height 160 cm. There was symmetrical partial ptosis. Her forehead was consrandy wrinkled, and her evebrows were elevated aboie the supraorbital ridges (fig. I ). Extraocular movements were full except for rnild impairment of up-gaze. The pupils were equal and reacted t o light as well as to acco~~iniodation. 'There was symmetrical weakness of the facial muscles. The pharyngeal reflex was present. Swallowing of solids and liquids was slow arid was iriterruptcd by coughing. T h e neck was thin, and neck flexors and st.ernocleidomastoid muscles were weak. Shoulder girdle, arms, and thighs were diffusely wasted. There was moderate symmetrical weakness (Grade 4 b y Medical Research Council criteria) of deltoids, supraspinati arid infrabpiriati, biceps, triceps, hip flexors, extensors, abductors, quadriceps, and hamstring muscles. Strength in distal muscle groups was preserved. Percussion and action myotonia was absent. T h e tendon reflexes of the legs were hypoactive. T h e patient's gait was cautious, heavy-footed, and waddling. An intraverious injection of
74
Myositis in Oculopharyngeal Dystrophy
10 mg of edrophonium chloride had no effect. Laboratory investigations showed normal levels of serum CK and aldolase. Contrast cineradiography of the esophagus demonstrated pooling of barium in the pyi-iforni sinus and irregular relaxation of the cricopharyngeus muscle. Tracheal aspiration of barium was noted with each attempt to swallow. Motor conduction velocity of the median nerve was normal (51 rnisec). Electromyographic stiidies of several proximal arm and leg rnuscles revealed normal resting activity and abundant brief, low-amplitude arid polyphasic motor unit potentials with early and full recruitment. Repetitive, supramaximal, three-per-second facial nerve stimulation failed to demonstrate a decrement of the orbicularis oculi muscle. A second muscle biopsy was obtaincd. MUSCLE BIOPSY FINDINGS
Paraffin-embedded, hematoxylin and eosin (H&E)and trichrome-stained sections of the initial quadriceps muscle biopsy demonstrated marked inflammatory alterations similar to those of polymyositis. Widespread fiber necrosis and phagocytosis were present, as were small, basophilic regenerating fibers with vesicular nuclei, occasional internal nuclei, and moderate variation in fiber size. Striking interstitial and rare perivascular infiltration with lymphocytes and histiocytes was present (fig. 2). Perifascicular atrophy and eridomysial fibrosis were not seen. After 15 months of treatment with prednisone, a second biopsy from the left deltoid muscle was obtained. Cryostat sections were processed by routine methods for light microscopy and histochemistry.6 Histogram, atrophy, and hypertrophy factors of type 1 and type 2 were calculated according to the method of Dubowitz and Brooke.6 The previously observed inflammatory changes were no longer evident. There were frequent small, angulated fibers that stained dark with the NADH-TR reaction, as well as occasional internal nuclei, rare degenerating and regenerating fibers, and prominent moth-eaten or whorled fibers. On H8cE stain, some fibers were seen to contain central or subsarcolernnial vacuoles surrounded by a basophilic rim. Both fiber types were involved. The histogram confirmed the visual impression of mild type 2 fiber atrophy (fig. 3). The findings of the second hiopsy were more consistent with the clinical picture of' oculopharyngeal dystrophy and possible superimposed corticosteroid myopathy. Prednisone was gradually tapered and discontinued. Two months later, the patient noted some functional improvement ir, walking, and her serum CK levels remainec normal.
MUSCLE & NERVE
Jan/Feb 1979
Figure 1 . Symrnetncal ptos/s with compensatory contracbon of frontahs muscle
hgure 2 ln/t/alquadnceps muscle b/opsy shows extenwe mtershtiai mf/mmatorytnfkation Paraffin section, hematoxylin & eosin Bar = I00
DISCUSSION
In some cases, the distinction between pol ym yositis and muscular dystrophy can be difficult to establish. In their critical review of' inflammatory myopathics, Bohan and Peter4 proposed four criteria, excluding the rash in dermatomyositis, by which polymyositis could be defined. Three of these criteria-weakness of limb-girdle muscles, elevation of serum CK, and muscle biopsy evidence of necrosis, regeneration, and in flammation-were initially met by our patient, although the distribution of weakness was atypical. Dysphagia is common, but the eye muscles are almost always spared in
Myositis in Oculopharyngeal Dystrophy
polymyositis or dermatomyositis. '4 case in which ophthalmoplegia was seen in dermatomyositi~'~ could have represented a patient with myasthenia gravis. Inlerstitial infhmmation and fiber necrosis indistinguishable from polymyositis are seen in almost 25% of muscle biopsies from rnyasthenic patient.~.~," 'This alternate diagnosis was rejected in our patient, since there was no fluctuation in weakness, no response to cholinergic drugs, and no decremental response to repetitive nerve stimulation. The family history and stereotyped clinical manifestations of our case were highly typical of oculopharyngeal dystrophy.
MUSCLE & NERVE
JanlFeb 1979
75
Fiber Type
1
2
Percentage 44 Mean Diometer ( g n l 6 2
56 42
SD AF HF
13
18
D 409
259 (43
-Y LL
0
lx 20-
m w
fz 10
-
L
0-9 10-
I
FIBER DIAMETER ( p m )
Figure 3 (A) Second deltoid muscle biopsy shows small angulated fibers and internal displacement of nuclei in large fibers A subsarcolemmal vacuole lined by a granular basophilic rim 1s seen in one anguiated fiber Cryostat sectfon, hematoxylin & eosin Bar = 50 g?i (8) Dark, angulated, and moth-eaten fibers Cryostat section, NADH-TR Bar = 50 g?i (C) Histogram shows increased variation fn hber size and type 2 fiber atrophy Hypertrophy factors (HF) for type 1 and atrophy factors (AF) for type 2 fibers are elevated
76
Myositis in Oculopharyngeal Dystrophy
We cannot exclude 1.he possibility that an independent, acquired polymyositis was superimposed on the genetic disorder, but this seems unlikely in light of the reported polym yositic reactions in other heritable muscular dystrophies.I6 In their series of progressive ophthalmoplegia, Rosenberg et all9 reported a similar patient with familial ptosis and ophthalmoplegia who developed limb-girdle weakness late in life, and whose biopsy showed evidence of polymyositis. Inflammatory cell in filtrations are not uncommon in muscular dystrophies. They have been reported in 36% of muscle biopsies from patients with various dystrophies, including Ihchenne muscular dystrophy,8 and in 50%'of patients with facioscapulohurneral dystrophy.'j .4n inflammatory Inyopathy of facioscapulohumeral distribution has been observed repeatedly.3~'4~'6.2u Some of these patients had dominantly inherited facioscapulohumeral dystrophy, while in others there was no family history of similar disease. Because of histopathologic similarities to idiopathic polymyositis, several of these patients were treated with prednisone. In a recent report,I3 six patients treated with prednisorie for periods ranging up to five years derived no long-term therapeutic benefit from it, although serum CK values were consistently lowered. The experience of our patient was similar. T h e inflammatory response in dystrophies has been related to a secondary immune response triggered by underlying muscle degeneration." Why an inflammatory response is present in some but not all cases of dystrophy is not yet known. The presence of inflammation both in idiopathic polyrnyositis and in miiscular dystrophy can create diagnostic problems. Histopathologically, hypertrophy of fibers favors a dystrophic myopathy:6 while extensive vacuolar liber degeneration and regeneration are more commonly encountered in polymyositis.* On the other hand, inorphologic criteria may overlap. In these situations, certain negative criteria'' (such as no family history of similar disease) may point toward a diagnosis of pol ymyositis. A positive family history of similar disease, as was seen in our patient, supports a diagnosis of secondary inflammation in an inherited disease; such a family history may also predict an unfavorable response to immunosuppressive therapy.
MUSCLE & NERVE
JaniFeb 1979
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