75 THE HISTOLOGY OF THE NEUROMUSCULAR JUNCTION Downloaded from https://academic.oup.com/brain/article/84/1/75/372729 by guest on 27 September 2021 IN DYSTROPHIA MYOTONICA BY VIOLET MACDERMOT Department of Neurology, St. Thomas' Hospital, London, S.E.I (1) INTRODUCTION DYSTROPJHC MYOTONICA is a familial disease affecting males and females, usually presenting in adult life, characterized by muscular wasting and weakness together with certain other features. The muscles mainly in- volved are the temporal, masseter, facial, sternomastoid and limb muscles, in the latter those mainly affected being peripheral in distribution. A widespread disorder of muscular contraction, myotonia, is also present but is noticed chiefly in the tongue and in the muscles involved in grasping. The other features of the condition are some degree of mental defect, dysphonia, cataracts, frontal baldness, sparse body hair and testicular atrophy. Any of the manifestations of the disease may be absent and the order of presentation of symptoms is variable. The myotonia may precede muscular wasting by many years or may occur independently. In those muscles which are severely wasted the myotonia tends to disappear. The interest of dystrophia myotonica lies in the peculiar distribution of muscle involvement and in the combination of a disorder of muscle function with endocrine and other dysplasic features. The results of histological examination of biopsy and post-mortem material have been described and reviewed by numerous workers, notably Steinert (1909), Adie and Greenfield (1923), Keschner and Davison (1933), Hassin and Kesert (1948), Wohlfart (1951), Adams, Denny-Brown and Pearson (1953), Greenfield, Shy, Alvord and Berg (1957). None of these investigators found conclusive evidence of involvement of the central nervous system. Examination of sections of muscle stained by usual methods showed in general that the characteristic feature of dystrophia myotonica was the presence of rows of centrally placed nuclei in otherwise intact muscle fibres. Other features such as atrophy and hypertrophy of muscle fibres, degeneration of muscle fibres, and increase in endomysial fibrous and fatty tissue appeared to be related to the later stages of the 76 VIOLET MACDERMOT disease, and were not obvious in many cases. It was noted by Adams et al. (1953) and by Greenfield et al. (1957) that the muscle fibres were particu- larly liable to fixation artefact. • It is noteworthy that little mention was made of changes in the intra- muscular nerve fibres until the introduction by Cogrs (1952a) of the intra- vital methylene-blue staining technique for muscle biopsy. In muscular dystrophy Bowden and Gutmann (1946) and Adams et al. (1953) found that the nerve fibres appeared normal. When the muscle fibres reached an advanced stage of degeneration, atrophic changes within the motor end- Downloaded from https://academic.oup.com/brain/article/84/1/75/372729 by guest on 27 September 2021 plates occurred, and finally with the disappearance of degenerate muscle fibres, long branches of the terminal nerve fibres were found ending blindly in the endomysial tissue. These workers used silver staining methods. Using the methylene-blue technique it was seen that abnormalities of the innervation pattern were present in dystrophia myotonica, which though similar to those seen in other myopathic disorders, showed certain charac- teristic features (Cogrs, 19526; Cogrs, 1955; Coers and Woolf, 1959). The nerve fibres within the intramuscular nerve bundles were said to be normal. The more distal nerve fibres were seen to show an unusual profusion of subtenninal nerve sprouts. The end-plates were noted to be large and well formed. Nerve fibres were described which ran parallel to muscle fibres and gave off short collateral sprouts. Another feature was the formation of a network of ramifying nerve fibres round individual muscle fibres. It is suggested that this axonal sprouting is secondary to the combined effects of degeneration and hypertrophy of the muscle fibres. In the present paper 10 cases of dystrophia myotonica are presented, the electromyographic and biopsy findings are described and an alternative suggestion is made as to the significance of the distal nerve changes. (2) TECHNIQUES (a) The technique of muscle biopsy using intra-vital methylene-blue to stain nerve fibres is described in detail by Coers and Woolf (1959). In the present series the deltoid was selected for biopsy in all cases and two adjacent strips of muscle were removed. Paraffin embedded sections cut at a thickness of 5-10/* were stained with haematoxylin and eosin, hsematoxylin and Van Gieson, and a trichrome stain. In addition, in order to demonstrate intramuscular nerve fibres further sections were stained as described by Bodian (1937) and Romanes (1950). Photographs of these sections were taken. Since the methylene-blue stained sections were cut at a thickness of 50-100^, the course of the distal nerve fibres as they travel in three dimensions between the muscle fibres was extremely difficult to record photographically. Drawings were therefore made of these sections, recording the appearances as two-dimensional diagrams. (b) Electromyography was carried out as described by Bauwens (1955) selecting various muscles {see Table I). Using a concentric needle electrode the muscle was explored and the pattern of electrical activity recorded at rest, on minimum and on full volition. In two cases no electromyography was done and in one case no record was made of the pattern obtained on volition. NEUROMUSCULAR JUNCTION IN DYSTROPHIA MYOTONICA 77 TABLE I.—ELECTROMYOORAPHY Cases 1 2 3 6 7 8-9 10 Muscles Abductor Flexor Biceps Deltoid Abductor Tibialis Deltoid Extensor explored pollicis carpi polllcis anterior carpi brevis ulnaris brevis ulnaris Biceps Extensor Flexor Brachio- Extensor Extensor digitorum carpi radialis digitorum digitorum communis ulnaris communis communis At rest High Downloaded from https://academic.oup.com/brain/article/84/1/75/372729 by guest on 27 September 2021 frequency discharges +++ + + + + + 0 On full volition Complete pattern +++ — + + + + Normal potentials + 00 — + 0 0 0 Reduced pattern 0 + 0— 0+ 0 + Low amplitude short duration potentials +++— 0 + + + NOTE.—Electromyography was not performed on Cases 4 and 5. (3) DESCRIPTION OF CASES Case 1.—A male aged 18 years first noticed symptoms in his 14th year. His maternal grandmother and mother had cataracts. Examination showed bilateral ptosis, temporal wasting and facial weakness. In the upper limbs the tendon reflexes were absent and the grasp was myotonic. Case 2.—A male aged 35 first noticed symptoms in his 18th year. His father and two brothers had cataracts. Examination showed low intelligence, frontal baldness, testicular atrophy and bilateral cataracts. The muscular system showed bilateral ptosis, temporal wasting, facial and palatal weakness, wasting and weakness of the sternomastoids and trapezii, and percussion myotonia of the tongue. The limbs showed generalized muscle wasting and weakness with depression of tendon reflexes and marked myotonia of grasp. Case 3.—A male aged 36 was first noticed to show symptoms in his first decade. His sister and possibly a maternal uncle were similarly affected. Examination showed imbecility, frontal baldness, absence of body hair, and a feminine distribution of fat, testicular atrophy, and bilateral cataracts. The muscular system showed temporal wasting, facial weakness, wasting and weakness of the sternomastoids and trapezii and wasting of the tongue. The limbs showed generalized muscle wasting and weakness most marked peripherally, with bilateral foot drop and absent tendon reflexes. The grasp was myotonic. Case 4.—A female aged 43, sister of Case 3, was probably first noticed to show symptoms in her second decade. Examination showed feeble-mindedness, frontal baldness, scanty body hair. There was facial weakness and wasting and weakness of the sternomastoids. The limbs showed generalised weakness most marked peripherally. The tendon reflexes were almost absent and the grasp was myotonic. 78 VIOLET MACDERMOT Case 5.—A female aged 44 was probably first noticed to show symptoms in her second decade. Her father, two paternal uncles and two brothers were similarly affected. Examination showed feeble-mindedness, frontal baldness. There was facial weakness and wasting and weakness of the sternomastoids. The limbs showed slight peripheral wasting and weakness, absent tendon reflexes and percussion myotonia of the thenar eminences. Case 6.—A male aged 49 first noticed symptoms in his 27th year. 6 out of his 9 brothers were similarly affected. Examination showed a speech defect, frontal baldness, feminine distribution of fat and body hair, bilateral cataract. There was Downloaded from https://academic.oup.com/brain/article/84/1/75/372729 by guest on 27 September 2021 facial weakness and wasting and weakness of the sternomastoids. The limbs showed peripheral wasting and weakness with absent tendon reflexes and a myotonic grasp. There was marked weakness of the trunk muscles. Case 7.—A female aged 50 first noticed symptoms in her third decade. No members of her family were known to be affected. Bilateral cataracts were removed at 33 years of age. Examination showed weakness of phonation, bilateral ptosis, temporal wast- ing, facial weakness, palatal weakness, wasting and weakness of the sternomastoids and myotonia of the tongue. The limbs showed generalized weakness most marked peri- pherally, with absent tendon reflexes