A patient with inclusion body myositis (IBM) is presented. Unusual aspects of this case include a myopathy of 36 years duration, severe dysphagia due to cricopharyngeus muscle dysfunction, improvement with cricopharyngeus myotomy, and a diagnostic cricopharyngeus muscle biopsy. Key words: inclusion body myositis cricopharyngeal muscle rimmed vacuoles dysphagia MUSCLE & NERVE 14:470-473 1991

INCLUSlON BODY MYOSITIS W I T H CRICOPHARYNGEUS MUSCLE INVOLVEMENT AND SEVERE DYSPHAGIA A. VERMA, MD, W.G. BRADLEY, DM, FRCP, A.M. ADESINA, MD, R. SOFFERMAN, MD, and W.W. PENDLEBURY, MD

I n 1971, under the title of "Inclusion Body Myositis" (IBM), Yunis and Samaha2* described a myopathy which clinically resembled a chronic myositis and pathologically showed the presence of characteristic vacuoles with fibrillary nuclear and cytoplasmic inclusions. Subsequently, IBM has been accepted as a distinct variety of idiopathic init 'difflammatory m y ~ p a t h y . ~ ~ ~ Clinically, ~'"~~~ ~ fers from polymyositis in the more frequent presence of distal weakness, a more chronic course, rare dysphagia, and poor response to corticosteroid therapy. We report a case of long-standing myopathy with severe dysphagia responding to cricopharyngeal myotomy. CASE REPORT

A 7 1-year-old woman had suffered limb weakness and atrophy for 29 years when first seen in the From the Departments of Neurology (Drs. Verma and Bradley), Pathology (Neuropathology) (Drs. Adesina and Pendlebury), and Surgery (Otolaryngology) (Dr Sofferman), University of Vermont College of Medicine, BurIington, Vermont. Acknowledgments: Dr. Ashok Verma was a visiting BOYCAST Fellow from the Department of Science and Technology, Government of India. He was also a recipient of an International Research Fellowship from the Fogarty International Center, NIH. Address reprint requests to Dr. Walter Bradley, Department of Neurology, University of Miami School of Medicine, PO Box 016960 (D4-5), Miami, FL 33101 Accepted for publication May 2, 1990. CCC 0148-639X/91/050470-04 $04.00 0 1991 John Wiley & Sons, Inc.

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UVM Neuromuscular Disease Clinic in 1981. At age 42, she had difficulty holding her arms above her head and was unable to go up stairs without the use of a handrail. The weakness remained stable for the next 25 years, but at age 67, she noted a progressive worsening of her limb weakness. By age 71 she was confined to a wheelchair. She denied pain or muscle twitching, and none of the members in her family had a similar disorder. Neurological assessment revealed proximal and distal muscle atrophy. Her limb strength was reduced diffusely to Medical Research Council (MRC) scale 3-415 in the upper limbs and 2-315 in the lower limbs with slight asymmetry. Deep tendon reflexes were sluggish in the upper limbs and absent in the lower limbs. Plantar responses were flexor and sensation was normal. At age 75 she started choking on both solid and liquid food. An upper gastrointestinal radiographic study showed a hiatal hernia with reflux and evidence of cricopharyngeal achalasia. Esophagoscopy in June 1985 showed a cricopharyngeal narrowing without fixed stricture. Several cricopharyngeal dilatations failed to relieve her symptoms. Laboratory investigations: normal CBC, CK 43 IUIL (normal 4 to 51 IU/L), SGOT 152 IU (normal 0 to 41), SGPT 213 I U (normal 0 to 45), serum alkaline phosphatase 152 IU (normal 38 to 126), total serum proteins 6.6 g/dL, and normal serum protein electrophoresis. Respiratory func-

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tion studies revealed a restrictive abnormality with FVC of 2.31 L (normal 2.99 L). Chest x-ray showed linear opaque streaks at the right base. Electrophysiological investigations revealed normal maximum evoked compound muscle action potentials and normal motor and sensory conduction (including F waves) studies in the upper and lower limbs. Monopolar needle examination showed a mixed neurogenic and myopathic pattern. There was polyphasia with a mild increase in amplitude of occasional motor units. Recruitment was mildly reduced. The average fiber density in single fiber EMG studies of the extensor digitorum communis muscle of the right forearm was 2.15 (normal 1.2). During the next three years, her swallowing became progressively worse, although her limb weakness was relatively stable. Biopsy from limb muscle was performed (see next section). At age 78, her dysphagia became critical, with choking and loss of weight. Barium-swallow-video study showed cricopharyngeal achalasia with aspiration. The peristalsis of the tubular esophagus was normal. Cricopharyngeal myotomy was performed. Her dysphagia improved markedly and at follow-up 8 months after myotomy she had gained back her original weight. MUSCLE BIOPSY STUDIES

A biopsy was obtained from the right biceps muscle for histochemical processing. There was marked variability in fiber size and shape with numerous round, and angulated atrophic fibers. No

FIGURE 2. Biceps biopsy showing inflammatory cell infiltration, increased endomysial and perirnysial connective tissue, and fiber size variability (hematoxylin-eosin, x 150).

small or large group atrophy was present. Some of the fibers contained vacuoles rimmed by basophilic granular material (Fig. 1) that stained red with modified Gomori trichrome, blue with NADH tetrazolium reductase, and red with periodic acid-Schiff reagent. Focal aggregates of mononuclear inflammatory cells were seen in the endomysial connective tissue and around vessels (Fig. 2). Muscle fiber necrosis with phagocytosis, and an increase in perimysial and endomysial connective tissue, were present. Occasional fibers with internalized nuclei and a moth-eaten pattern were identified. Myosin ATPase stains showed poor fiber type differentiation. Electron microscopy showed occasional intranuclear and intrasarcoplasmic filaments measuring about 20 nm in thickness (Fig. 3A and B). Prominent subsarcolemmal and intermyofibrillar accumulations of degenerative myeloid structures, focal areas of Z-band streaming, and tubular aggregates were present. Portions of the omohyoid and cricopharyngeus muscles were obtained at the time of the cricopharyngeal myotomy. They showed loss of fibers, prominent rimmed vacuoles, extensive fiber necrosis with phagocytosis, mononuclear inflammatory cell infiltration, and increased endomysial connective tissue (Fig. 4). DISCUSSION

FIGURE 1. Cryostat section of right biceps muscle showing some of the fibers containing irregular vacuoles rimmed by granular material (hematoxylin-eosin, ~300).

Inclusion Body Myositis

The patient had inclusion body myositis (IBM) based on the presence of muscle inflammation, rimmed vacuoles, and intranuclear and cytoplasmic 20-nm diameter filaments. In oculopharyn-

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FIGURE 3. Electron micrograph showing muscle fibers with (A) intranuclear filaments (x5250), and (B) intrasarcoplasmic filaments measuring about 20 nm in thickness and some myeloid degenerative material ( x 12000).

geal muscular dystrophy rimmed vacuoles and intranuclear filaments can also be seen,9 and rarely there may be inflammation.' However, there was no ocular muscle weakness in our patient, no family history, and the pattern of limb muscle weakness was atypical for that of oculopharyngeal muscular dystrophy. Our patient is of particular interest because of the long duration (36 years) of myopathic symptoms resembling a limb girdle dystrophy. The incidence of dysphagia among patients with inflammatory myopathy other than IBM has been reported to be 12% to 31% in large se-

FIGURE 4. Cryostat section of cricopharyngeus muscle showing mononuclear inflammatory cell infiltration and considerable increase in endomysial connective tissue (hematoxylin-eosin, x150).

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ries. 1 3 , I7 Physiological studies of esophageal function suggest a higher frequency of involvement in myositis." In a review of 40 previously reported cases of IBM, Sunohara et all9 found dysphagia in 5 patients. Dysphagia may arise from several causes in polymyositis. A decrease in the strength of pharyngeal muscles, disordered motility of esophagus, vallecular pooling, and tongue weakness may all interfere with normal swallowing.l 1 Cricopharyngeus muscle dysfunction or cricopharyngeal achalasia is an easily overlooked entity that has received attention in recent otolaryngologic literature as a distinct disorder of swallowing. Abnormalities of crico haryngeal function have been linked with age, 1 Y neurological diseases, l4 reflux,8 as well as other causes including ~ u r g e r y .'The ~ syndrome of cricopharyngeal dysfunction has also been reported in cases of pol myositis,62"' and dermatomyositis.16 Kagan et all' reported 3 cases of cricopharyngeal obstruction due to cricopharyngeal achalasia, in whom radiographic studies done at the onset of the polymyositis, prior to the development of dyspha ia, showed no evidence of achalasia. Wintzen et ' a! recently reported 4 elderly patients with IBM with dysphagia, in 3 of whom the dysphagia preceded limb muscle weakness by u p to 7 years. It has been suggested that dysphagia in myositis is due to inflammation and edema of cricopharyngeus muscle and fibrosis of esophageal inlet mechanism. Histologic evidence of muscle inflammation has been documented in the segment excised at the time of cricopharyngeal myotomy in

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polymyositis.”12,’”.20 Our patient appears to be the first case of severe dysphagia due to cricopharyngeal involvement in IBM in whom the histology of the cricopharyngeus muscle has been studied; we found changes similar to, but more severe than those in the limb muscle. Recognition of cricopharyngeal obstruction is important for two reasons. First, recurrent aspira-

tions of food into the airways may lead to death. Second, the syndrome, if severe, may be treated with cricopharyngeal myotomy, which offers a chance of amelioration of symptoms. Our IBM patient, and 3 of the 4 IBM patients reported by Wintzen et alZ1 had a marked improvement in swallowing following the myotomy.

REFERENCES 1. Bohan A, Peter JB, Bowman RL, Pearson CM: A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medzczne 1977; 56:255-286. 2. Bosch EP, Govans JDC, Munsat 7‘:Inflammatory myopathy in oculopharyngeal dystrophy. Muscle Nerve 1979; 2:73-77. 3. Bradley WG, Tandan R. Inflammatory disease of muscle, in Kelley WW, Harris Ed, Ruddy S, Sledge CB (eds): Textbook of Rheumatology, 3 Ed. Philadelphia, WB Saunders, 1989, pp 1263- 1287. 4. Carpenter S, Karpati B, Heller I , Eisen A: Inclusion body myositis: a distinct variety of inflammatory myopathy. Neurology 1978; 28:8- 17. 5. Chad D, Good P, Adelman L, Bradley WG, Mills J: Inclusion body myositis associated with Sjogren’s syndrome. Arch Neurol 1982; 39:186- 188. 6. Dietz F, Logernan JA, Sahgal V, Schmid FR: Cricopharyngeal muscle dysfunction in the differential diagnosis of dysphagia in polymyositis. Arthrztis Rheuma 1980; 23:491495. 7. Ellis FH J r : Upper esophageal sphincter in health and disease. Surg Clan North A m 1971; 51:553-565. 8. Henderson RD, Woolf C, Marryatt G: Pharyngoesophageal dysphagia and gastroesophageal reflux. iaryngosiope 1976; 86:1531-1539. 9. Huhner G, Pongratz D: Inclusion body myositis: an example of diagnostic electron microscopy. Biol Cell 1980; 39:283-286. 10. Jacob H, Berkowitz D, McDonald E, Bernstein LH, Beneventano T: T h e esophageal motility disorder of polymyositis. Arch Intern Med 1984; 143:2262-2264. 11. Kagan LJ: Polymyositis/dermatornyositis, in McCarthy DJ (ed): Arthritis and Allied Conditions. 10 Ed. Philadelphia, Lea & Febiger, 1984, pp 971-993.

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12. Kagan LJ, Hochman RB, Strong EW: Cricopharyngeal ohstruction in inflammatory myopathy (polyinyositisidei-rIlatomyositis). Report of three cases and review of literature. Arthritis Rheuma 1985; 28:630-636. 13. Mikol J : Inclusion body inyositis, in Engel AG, Banker BQ (eds): Myology, Vol 2. New York, McGraw-Hill, 1986, pp 1423- 1438. 14. O’Connor AF, Adrian GM: Cineflurography in the diagnosis of pharyngeal palsies. J Laryngol Otol 1976; 90:10151019. 15. Pitcher JL: Dysphagia in the elderly: causes and diagnosis. Geriatrics 1973; 28:64-69. 16. Porubsky ES, Murray JP, Pratt LL: Cricopharyngeal achalasia in dermatomyositis. Arch Otorhinolaryngol 1973; 98:428-429. 17. Ringel SP, Kenny CE, Neville HE, Giorno R, Carry MR: Spectrum of inclusion body myositis. Arch Neurol 1987; 44: 1154- 1157. 18. Sawchak ] A , Kula RW, Sher JH, Shafig SA, Clark LM: Clinicopathologic investigations in patients with inclusion body myositis (IBM). Neurology 1983; 33(suppl):237. 19. Sunohara N , Nonaka I , Kamai N, Satoyashi E: Distal myopathy with rimmed vacuole formation. A follow-up study. Brain 1989; 112:65-84. 20. Thomas FB, Lehauer S, Greenherger NJ: Polyniyositis masquerading as carcinoma of the cervical esophagus. Arch Int Med 1972; 129:984-986. 21. Wintzen AR, Bots ATAM, DeBaker HM, Hulshof J H , Padberg GW: Dysphagia in inclusion body myositis.1 Neurol Neurosurg Psychiatry 1988; 51K:1542- 1545. 22. Yunis EJ, Samaha FJ: Inclusion body myositis. Lab Invest 1971: 25:240-248.

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Inclusion body myositis with cricopharyngeus muscle involvement and severe dysphagia.

A patient with inclusion body myositis (IBM) is presented. Unusual aspects of this case include a myopathy of 36 years duration, severe dysphagia due ...
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