Journal o['the neurological Sciences, 1974, 21 : 165-169 165 :(: Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands

Oculopharyngeal Muscular Dystrophy A Case with A b n o r m a l M i t o c h o n d r i a and "Fingerpr int" Inc lus ions

J. JULIEN, CL. VITAL, J. M. VALLAT, M. VALLAT AND M. LE BLANC

Neurology Department, Hfpitat Saint-Andrk, Bordeaux, and Electron Microscopy Centre, Talence 33 (France)

(Received 3 September, 1973)

INTRODU CTION

In 1962, Victor, Hayes and Adams called attention to "oculopharyngeal dystrophy", which is an unusual form of ocular myopathy with onset late in life and associated with dysphagia. Since then, several clinical and histological examples (Peterman, Lillington and Jampis 1964; Bray, Kaarsoo and Ross 1965; Zintz 1966; Rebeiz, Caulfield and Adams 1969; Warter, Stoebner, Stephan and Isch 1969) have been reported so that it has been confirmed that this disorder is dystrophic and not due to a primary degeneration of motor neurons. However, there are few data available on the appearance of muscle biopsies of such patients as studied under the electron microscope (Zintz 1966; Rebeiz et al. 1969; Warter et al.1969). It is for this reason that we are encouraged to add the present case report.

CASE REPORT

Mr. M... born in 1904, was first seen in 1972. Slowly progressive ptosis had started at the age of 40 years. Since the age of 55, he had dysphagia which had progressed slowly. According to the patient, several other members of the family were suffering from the same kind of neurological disorder. One of his brothers died at the age of 60, from difficulty in swallowing. A daughter, 45 years old, was available for examination : she had bilateral ptosis only.

The most striking feature of physical examination was the ptosis so that the palpebral fissures were almost completely obliterated; no voluntary elevation of the lids could be accomplished despite a reason- ably vigorous contraction of the frontalis muscles. There was also a slight degree of weakness of the orbicu- laris oculi and the masseters were thinned. All the extraocular muscles were very weak, so that the oph- thalmoplegia was bilateral and almost complete, The pupillary reactions were normal and the fundi showed no significant changes.

Although the patient had great difficulty in swallowing and his speech had become progressively less distinct, there was no observable defect of the pharynx or hypopharynx.

Otherwise, neurological examination revealed marked and generalized thinness, with only a moderate weakness of the proximal muscles of the upper limbs. The tendon reflexes were normal. Sensory function was normal and there were neither fasciculations nor myotonia.

Reprint requests to J. M. Vallat, H6pital Saint-Andre, 1 rue Jean Burguet, Bordeaux 33 (France).

166 OCULOPHARYNGEAL MUSCULAR DYSTROPHY

The serum aldolase, glutamic--oxaloacetic transaminase and creatine phosphokinase levels a,c~ e mwmal, Lumbar puncture yielded normal cerebrospinal fluid ira all respects.

The electromyographic findings were consistent with a myopathic disorder m externzg ov-uktr and limi'~ muscles.

The right deltoid muscle was biopsied

MATERIAL AND METHODS

Portions of the biopsy specimen were fixed in 10°/,i buffered formaldehyde solution: Paraffin-embedded sections were stained with hematoxylin-eosin: For electron microscopy, other portions of the biopsy specimen were fixed in phosphate-buffered 5~o glutaraldehyde, post-fixed in osmium tetroxide, dehydrated and embedded in epoxy resin. Thin sections were stained with uranyl acetate and lead citrate prior to examination in the electronmicroscope.

RESULTS

By light microscopy, the changes were slight and consistent with the diagnosis of myopathy; there was some variation in the size of muscle fibres and a few areas of sarcolemmal nuclear proliferation.

By electron microscopy, there were two principal types of change: in manY myo- fibres, the mitochondria were morphologically very abnormal; there were clusters of abnormally large and bizarrely structured mitochondria, containing lipid droplets or

Fig. 1. A cluster of abnormally large mitochondria. Some of them have their central cristae replaced by paracrystalline material (longitudinal section).

J. JULIEN, CL. VITAL, J. M. VALLAT, M. VALLAT, M. LE BLANC 167

Fig. 2. Muscle fibre containing a "fingerprint inclusion" on the left (longitudinal section),

Fig. 3. Subarcolemmal structure composed of concentric lamellae arrayed in "'fingerprint patterns" (longitudinal section).

168 OCULOPHARYNGEAL MUSCULAR DYSTROPHY

paracrystalline structures (Fig. 1 ). These aggregates were often subsarcolemmat, but sometimes randomly scattered in the sarcoplasm where they destroyed the myofibrils; in these same fibres or in others, several abnormal inclusions were observed (Figs. 2, 3). They were oval or circular, always subsarcolemmal and frequently juxtanuclear, and often surrounded by several normal mitochondria. These abnormal structures looked very much like those described by Engel, Angelin and Gomez (1972): they varied from 1,75 #m to 3,8 #m in length and from 0,75 #m to 1,4 #m in width. "Typi- cally they were composed of complex, convoluted lamellae arranged in fingerprint patterns. The pattern of the convolutions varied in different parallel planes of the same inclusion and from one inclusion to another". At higher magnification, these lamellae were studded with "sawtooth-like" projections.

DISCUSSION

There is no doubt that the clinical and histological findings in our case were typical of oculopharyngeal dystrophy. Three similar observations have already been studied under the electron microscope. In the first case described by Rebeiz et at, (1969) the observations were only made on a small portion of one eye muscle and the changes did not differ from those seen in controls.

The illustrations published by Zintz (1966) and by Warter et al. (1969) showed abnormal mitochondria which were similar to those described in the present report. Such morphologically abnormal mitochondria in muscle cells have been reported in a variety of circumstances which were reviewed by Olson, Engel, Walsh and Ein- augler (1972) who described them in several cases of "ophthalmoplegia plus", a syndrome which was identified by Drachmann in 1968.

Other cases have been studied extensively enough to suggest that most cases of pure ocular myopathy show structural changes in muscle mitochondria (Zintz 1967: Aubert, Arroyo, Albatro and Detolle 1968; Castaigne, Laplane, Fardeau, Dordain, Autret and Hirt 1972; Vallat, Castel, Vallat, Lerebeller, Vital and Leman 1972).

In our patient we have observed another ultrastructural anomaly which looks much like that described by Engel et al. (1972) in a case of non-progressive congenital myopathy without any involvement of the facial, ocular and pharyngeal muscles. They called this congenital muscle disease "fingerprint body myopathy". These structures are composed of concentric lamellae arranged in "fingerprint patterns": they have been found infrequently in several muscular diseases: viz. congenital myopathy (Engel et al. 1972), dermatomyositis (Carpenter, Karpati, Eigem Ander- mann and Waters 1972), d ystrophia myotonica (Tome and Fardeau t973) but never in the ocular myopathies. It must therefore be concluded that the presence of such structures in several different muscle diseases and in the present case, cannot be regarded as a specific morphological feature.

SUMMARY

A typical case of oculopharyngeal muscular dystrophy is reported. On electron microscopic study of a deltoid muscle biopsy, abnormal mitochondria and "finger-

J. JULIEN, CL. VITAL, J. M. VALLAT, M. VALLAT, M. LE BLANC 169

print" inclusions were observed in numerous muscle fibers. The inclusions were composed of concentric lamellae of short electron-dense linear elements. Identical structures have been reported ila three other myopathic disorders so that they cannot be regarded as a specific morphologic feature.

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