Journal o['the Neurologieal Scienees, 1977, 33 : 453-460 c) Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
ACUTE VIRAL POLYMYOS1TIS WITH PREDOMINANT INVOLVEM ENT
453
DIAPHRAGM
J. DE REUCK, W. DE COSTER and N. INDERADJAJA Neuropathology Unit, Departments of" Neurology (ProJ~ H. Vonder Eecken) and Pathology (ProJl H. Roels'), University Hospital, Ghent (Belgium)
Received 22 March, 1977)
k
_
SUMMARY A 20-month-old mentally retarded girl developed an acute upper respiratory infection, followed by breathing difficulties, leading to death. Picorna virus-like particles were demonstrated in a mildly affected quadriceps femoris muscle biopsy, while the necropsy findings demonstrated an acute polymyositis with predominant diaphragm involvement. The mental retardation was due to micropolygyria o f the brain. Initial respiratory difficulties are an u n k n o w n feature of polymyositis. In this case the upper respiratory infection, possibly caused by a Coxsackie Be, is evoked as responsible for this unusual distribution of the acute viral polymyositis.
INTRODUCTION Initial respiratory difficulties, due to predominant involvement o f the diaphragm muscle are u n k n o w n in polymyositis (Eaton 1954; Walton and A d a m s 1958; Pearson and Rose 1960; Barwick and W a l t o n 1963). They are, however, described in other neuromuscular diseases, such as in neonatal myotonic dystrophy (Aicardi, Conti and Gouti6res 1974; Bossen, Shelburne and Verkauf 1974), in acute parathion intoxication (De Reuck and Willems 1975) and in some congenital myopathies (De Reuck, Hooft, De Coster, Vanden Bossche and Cuvelier 1977). The present study illustrates the possibility of a more or less selective vulnerability of the diaphragm to a viral agent. CASE REPORT A 20-month-old mentally retarded girl was admitted to the paediatric department because 5 days earlier she had developed high fever of 39 C with coughing fits and abundant phlegm. She had been treated with sulfonamides and penicillin for an acute tonsillitis. For the next few days the infant remained ill, although the fever had decreased. On admission she was pale and hypotonic, with a facial rash, tonsillitis and an enlarged liver. Heart and lung auscultation was normal. She weighed 9 kg and
454 the head circumference was 47.7 cm. The tendon reflexes were absent. On the 3rd day after admissions, she was put on a respirator because of increasing breathing difficulties, although the chest X-ray showed no abnormalities. The sedimentation rate, the number of leucocytes in blood and the muscle serum enzymes were markedly elevated. Serum antibodies were 1/8 for Coxsackie B1 and 1/64 for Coxsackie Bo,.A muscle biopsy was performed the next day, just prior to her decease.
Material and methods Pieces of the right quadriceps femoris muscle were obtained, and examined with light-microscopic and histochemical stains and with the electron microscope. The general post-mortem examination was performed 24 hr after death and a large number of muscle samples were taken. RESULTS
Biopsy findings The light-microscopic examination of the right quadriceps femoris muscle revealed only mild lesions. Most muscle fibres were unaffected with preserved crossstriation of the myofibrils and excentrically located sarcolemmical nuclei. There was only mild variation in muscle fibre size. Occasionally waxy necrosis and lytic fibres, invaded by macrophages and lymphocytes were observed. Around some blood vessels and in the interstitial connective tissue a few scattered infiltrates of lymphocytes and plasma cells were present. The nerves had a normal appearance. The histoenzymatic examination showed a clear differentiation into 2 muscle fibre types. Only a few fibres had a "moth-eaten" appearance and in some invaded by inflammatory cells acid phosphatase activity could be demonstrated. The electron-microscopic examination also showed a large number of muscle fibres with a normal appearance. In some fibres, however, the columns of myofibrils were interrupted at the level of the A/I junction and only fragments of the A-band were left. The remaining Z-discs were preserved, without streaming. These fibres were devoided of glycogen granules and had lost the major part of their sarcoplasmic reticulum (Fig. 1). Only some small triads and a few small electron-dense mitochondria were present. The basal lamina and the sarcolemma were preserved. Some other fibres showed a complete disorientation of the myofilaments with disappearance of the Zdiscs, while the M-bands were still present. These fibres had lost their sarcolemma and contained some dense granular vesicles, which were sometimes grouped together, surrounded by a c o m m o n membrane, with the appearance of multi-vesicular bodies. In some fibres the alterations were more profound and varied from severe disintegration to complete absence of myofilaments. They were sometimes invaded by macrophages and activated lymphocytes (Fig. 2). However, some of the dense cellular profiles were reminiscent of satellite cells. In a few quite normal-looking cross-sectioned fibres, subsarcolemmic paracrystalline inclusions were present. These inclusions were not surrounded by a distinct membrane and were not connected to the membranous systems of the muscle fibres. They had an internal periodicity of approximately 21-23 nm. Their size depended upon the level of section and varied from 0.9 to 5.0/zm (Fig. 3). Necropsy findings General post-mortem examination showed oedema and congestion of the lungs,
455
Fig. 1. The columns of myofibrils near the sarcolemma are interrupted at the level of the A/I junctions. Only fragments of the A-band are preserved. Glycogen granules and sarcoplasmic reticulum are lost. ,< 10,800.
456
Fig. 2. Complete disintegration and absence of myofibrils in this muscle fibre, invaded by a macro,phage and an activated lymphocyte. The basal lamina surrounds the inflammatory cells while the sarcolemma is absent. The filamentous material in the bottom half of the figure is the remains of myofibrils. :~ 13,200.
an immunoreactive spleen and a fatty liver. The heart muscle and skin were normal. The fresh brain weighed 1225 g and many areas of micropolygyria were present both in the cerebral and the cerebellar cortex. The most severely affected muscle appeared to be the diaphragm. The majority of the muscle fibres showed a variable degree of degeneration and necrosis: many areas of waxy degeneration, fragmentation, lysis and phagocytosis with clumps of pyknotic sarcolemmic nuclei were present (Fig. 4). Some fibres had a basophilic sarcoplasm with a large number of swollen vesicular nuclei on H and E staining. There was extensive variation of muscle fibre size. Large infiltrations of lymphocytes, plasma cells and macrophages were present in the interstitial connective tissue and around some veins. The arteries appeared normal. The connective tissue was mildly increased. The nerve endings were fragmented in the vicinity of degenerative muscle fibres. In the left seventh intercostal muscle and in the left sternocleidomastoideus muscle the described lesions above were less pronounced. In the left quadriceps femoris and gastrocnemius muscles the inflammatory reaction and the muscle fibre degeneration were less distinct, while in the left deltoid and biceps brachii muscles only discrete lesions were observed (Fig. 5). The left levator palpebrae superioris muscle was not affected.
Fig. 3. Paracrystalline inclusions with an internal periodicity of 21-23 nm are present, in the subsarcolemmic region. ;'; 39,000.
Fig. 4. Longitudinal section of the diaphragm. Most muscle fibres show waxy degeneration and lysis with invasion by lymphocytes, plasma cells and macrophages. Some basophylic fibres with swollen vesicular sarcolemmic nuclei are also present. The connective tissue is mildly increased. H and E; × 400.
458
Fig. 5. The degenerative changes and the inflammatory reaction are severe in the diaphragm (A), less pronounced in the sternocleidomastoid (B), moderate in the quadriceps femoris (C) and mild in 1he deltoideus muscle (D). H and E; "~ 160. DISCUSSION The clinical history a n d the biopsy and necropsy findings argue that the acute respiratory difficulties were due to a n acute polymyositis with p r e d o m i n a n t involvem e n t of the diaphragm. The pre-existing delayed developmental milestones in this
459 child can be related to the m a l f o r m a t i o n o f the central nervous system. R e s p i r a t o r y d i s o r d e r s occur in only 2 % of cases of polymyositis a n d even in a terminal stage o f m o r e generalized i n v o l v e m e n t they are extremely rare, unless a very acute myolytic process exists f r o m the start or a coexistent m a l i g n a n c y makes the muscular disease refractory to c o r t i c o s t e r o i d t h e r a p y (Pearson a n d Currie 1974). In the biopsy o f this case paracrystalline structures were found, which were similar to those described by C h o u a n d G u t m a n n (1970) a n d which were t h o u g h t to be Picorna virus-like particles. They were different f r o m other virus-like structures, such as the myxovirus-like structures ( C h o u 1968; F i d z i a n s k a 1973) a n d the filamentous inclusion bodies (Yunis a n d S a m a h a 1971). The aggression to the muscle fibres by activated l y m p h o c y t e s a n d m a c r o p h a g e s followed by disintegration o f the s a r c o l e m m a has been shown in polymyositis (Hughes a n d Esiri 1975), but is r e p o r t e d in cases o f t u r n o u t cells t r a n s p l a n t e d into striated muscle (Bab~i 1976). The histological a p p e a r a n c e o f the d i a p h r a g m in this case resembled the acute myolysis observed in muscles of the n e w b o r n infected by a Coxsackie virus ( F r e u d e n b e r g , R o u l e t a n d Nicole 1952), which is spread by the upper r e s p i r a t o r y tract. Coxsackie virus-like particles in muscles have been f o u n d in cases o f polymyositis ( M a s t a g l i a a n d W a l t o n 1970) a n d resemble " n a k e d " R N A Picorna viruses (Melnick, C o c k b u r n , Dallfdorf, G a r d , G e a r , M c H a m m o n , K a p l a n , Nagler, O k e r - B l o m , Rhodes, Sabin, Verlinde a n d von M a g n u s 1963). Polymyositis in which Picorna viruses are d e m o n s t r a t e d has a m o r e acute clinical course t h a n t h a t in which other virus-like particles ( C h o u 1973) are seen. A l t h o u g h no viral isolation h a d been p e r f o r m e d in the present case, there is some evidence to relate this p a r t i c u l a r muscular d i s o r d e r to an acute Coxsackie B2 virus infection.
REFERENCES Aicardi, J., D. Conti and E. Gouti6res (1974) Les formes n6onatales de la dystrophie myotonique de Steinert, J. neurol. Sci., 22:149 164. Babel, F. (1976) Etude ultrastructurale sur la pathog6nie du muscle stri6 par des tumeurs transplantables, J. Ultrastruet. Res., 56: 287-303. Barwick, D. D. and J. N. Walton (1963) Polymyositis, Amer. J. Med., 35:646 660. Bossen, E. H., J. D. Shelburne and B. S. Verkauf (1974) Respiratory muscle involvement in infantile myotonic dystrophy, Arch. Path., 97:250 252. Chou, S. M. (1968) Myxovirus-like structures and accompanying nuclear changes in chronic polymyositis, Areh. Path., 86: 649-658. Chou, S. M. (1973) Prospects of viral etiology in polymyositis. In: B. A. Kakulas (Ed.), Proceedings of the 2nd International Congress on Muscle Diseases, Perth, Australia, 1971, Part 2 (Clinical Studies hi Myology) (International Congress Series, No. 295), Excerpta Medica, Amsterdam, 1973, pp.
17-28. Chou, S. M. and L. Gutmann (1970) Picorna virus-like crystals in subacute polymyositis, Neurology (Minneap.), 20 : 205-213. De Reuck, J. and J. Willems (1975) Acute parathion poisoning - - Myopathic changes in the diaphragm, J. Neurol. (Berl.), 208: 309-314. De Reuck, J., C. Hooft, W. De Coster, H. Vanden Bossche and C. Cuvelier (1977) A progressive congenital myopathy - - Initial involvement of the diaphragm with Type I muscle fiber atrophy, Europ. Neurol., 15:217-226. Eaton, L. M. (1954) The perspective of neurology in regard to polymyositis, Neurology (Minneap.), 4 : 245-263.
460 Fidzianska, A. (1973) Virus-like structures in muscle in chronic polymyositis, Acta neuropath. ( Ber/. ,. 23: 23-31. Freudenherg, E., F. Roulet and R. Nicole (1952) Kongenitale Infection mit Coxsackie-Virus, Am~. paediat. (Basel), 178:150 161. Hughes, J. T. and M. M. Esiri (1975) Ultrastructural studies in human polymyositis, J. neurol. Sci.. 25 : 347-360. Mastaglia, F. L. and J. N. Walton (1970) Coxsackie virus-like particles in skeletal muscle from a case of polymyositis, J. neurol. Sci., 11 : 593-599. Melnick, J. L., W. C. Cockburn, G. Dalldorf, S. Gard, J. H. Gear, D. W. McHammon, M. M. Kaplan, F. P. Nagler, N. Oker-Blom, A. J. Rhodes, A. B. Sabin, J. D. Verlinde and H. Von Magnus (International Enterovirus Study Group) (1963) Picorna virus group, Virology, 19: 114-116. Pearson, C. M. and A. S. Rose (1960) Myositis ---The inflammatory disorders of muscle, Res. Publ. Ass. Res. Nerv. Ment. Dis., 38: 422~478. Pearson, C. M. and S. Currie (1974) Polymyositis and related disorders. In: J. N. Walton (Ed.), Disorders o f Voluntary Muscle, Churchill, Edinburgh, pp. 614-652. Walton, J. N. and R. D. Adams (1958) Polymyositis, Livingstone, Edinburgh. Yunis, E. J. and F. J. Samaha (1971) Inclusion body myositis, Lab. Invest., 25: 240-248.
ACUTE VIRAL POLYMYOS1TIS WITH PREDOMINANT INVOLVEM ENT
453
DIAPHRAGM
J. DE REUCK, W. DE COSTER and N. INDERADJAJA Neuropathology Unit, Departments of" Neurology (ProJ~ H. Vonder Eecken) and Pathology (ProJl H. Roels'), University Hospital, Ghent (Belgium)
Received 22 March, 1977)
k
_
SUMMARY A 20-month-old mentally retarded girl developed an acute upper respiratory infection, followed by breathing difficulties, leading to death. Picorna virus-like particles were demonstrated in a mildly affected quadriceps femoris muscle biopsy, while the necropsy findings demonstrated an acute polymyositis with predominant diaphragm involvement. The mental retardation was due to micropolygyria o f the brain. Initial respiratory difficulties are an u n k n o w n feature of polymyositis. In this case the upper respiratory infection, possibly caused by a Coxsackie Be, is evoked as responsible for this unusual distribution of the acute viral polymyositis.
INTRODUCTION Initial respiratory difficulties, due to predominant involvement o f the diaphragm muscle are u n k n o w n in polymyositis (Eaton 1954; Walton and A d a m s 1958; Pearson and Rose 1960; Barwick and W a l t o n 1963). They are, however, described in other neuromuscular diseases, such as in neonatal myotonic dystrophy (Aicardi, Conti and Gouti6res 1974; Bossen, Shelburne and Verkauf 1974), in acute parathion intoxication (De Reuck and Willems 1975) and in some congenital myopathies (De Reuck, Hooft, De Coster, Vanden Bossche and Cuvelier 1977). The present study illustrates the possibility of a more or less selective vulnerability of the diaphragm to a viral agent. CASE REPORT A 20-month-old mentally retarded girl was admitted to the paediatric department because 5 days earlier she had developed high fever of 39 C with coughing fits and abundant phlegm. She had been treated with sulfonamides and penicillin for an acute tonsillitis. For the next few days the infant remained ill, although the fever had decreased. On admission she was pale and hypotonic, with a facial rash, tonsillitis and an enlarged liver. Heart and lung auscultation was normal. She weighed 9 kg and
454 the head circumference was 47.7 cm. The tendon reflexes were absent. On the 3rd day after admissions, she was put on a respirator because of increasing breathing difficulties, although the chest X-ray showed no abnormalities. The sedimentation rate, the number of leucocytes in blood and the muscle serum enzymes were markedly elevated. Serum antibodies were 1/8 for Coxsackie B1 and 1/64 for Coxsackie Bo,.A muscle biopsy was performed the next day, just prior to her decease.
Material and methods Pieces of the right quadriceps femoris muscle were obtained, and examined with light-microscopic and histochemical stains and with the electron microscope. The general post-mortem examination was performed 24 hr after death and a large number of muscle samples were taken. RESULTS
Biopsy findings The light-microscopic examination of the right quadriceps femoris muscle revealed only mild lesions. Most muscle fibres were unaffected with preserved crossstriation of the myofibrils and excentrically located sarcolemmical nuclei. There was only mild variation in muscle fibre size. Occasionally waxy necrosis and lytic fibres, invaded by macrophages and lymphocytes were observed. Around some blood vessels and in the interstitial connective tissue a few scattered infiltrates of lymphocytes and plasma cells were present. The nerves had a normal appearance. The histoenzymatic examination showed a clear differentiation into 2 muscle fibre types. Only a few fibres had a "moth-eaten" appearance and in some invaded by inflammatory cells acid phosphatase activity could be demonstrated. The electron-microscopic examination also showed a large number of muscle fibres with a normal appearance. In some fibres, however, the columns of myofibrils were interrupted at the level of the A/I junction and only fragments of the A-band were left. The remaining Z-discs were preserved, without streaming. These fibres were devoided of glycogen granules and had lost the major part of their sarcoplasmic reticulum (Fig. 1). Only some small triads and a few small electron-dense mitochondria were present. The basal lamina and the sarcolemma were preserved. Some other fibres showed a complete disorientation of the myofilaments with disappearance of the Zdiscs, while the M-bands were still present. These fibres had lost their sarcolemma and contained some dense granular vesicles, which were sometimes grouped together, surrounded by a c o m m o n membrane, with the appearance of multi-vesicular bodies. In some fibres the alterations were more profound and varied from severe disintegration to complete absence of myofilaments. They were sometimes invaded by macrophages and activated lymphocytes (Fig. 2). However, some of the dense cellular profiles were reminiscent of satellite cells. In a few quite normal-looking cross-sectioned fibres, subsarcolemmic paracrystalline inclusions were present. These inclusions were not surrounded by a distinct membrane and were not connected to the membranous systems of the muscle fibres. They had an internal periodicity of approximately 21-23 nm. Their size depended upon the level of section and varied from 0.9 to 5.0/zm (Fig. 3). Necropsy findings General post-mortem examination showed oedema and congestion of the lungs,
455
Fig. 1. The columns of myofibrils near the sarcolemma are interrupted at the level of the A/I junctions. Only fragments of the A-band are preserved. Glycogen granules and sarcoplasmic reticulum are lost. ,< 10,800.
456
Fig. 2. Complete disintegration and absence of myofibrils in this muscle fibre, invaded by a macro,phage and an activated lymphocyte. The basal lamina surrounds the inflammatory cells while the sarcolemma is absent. The filamentous material in the bottom half of the figure is the remains of myofibrils. :~ 13,200.
an immunoreactive spleen and a fatty liver. The heart muscle and skin were normal. The fresh brain weighed 1225 g and many areas of micropolygyria were present both in the cerebral and the cerebellar cortex. The most severely affected muscle appeared to be the diaphragm. The majority of the muscle fibres showed a variable degree of degeneration and necrosis: many areas of waxy degeneration, fragmentation, lysis and phagocytosis with clumps of pyknotic sarcolemmic nuclei were present (Fig. 4). Some fibres had a basophilic sarcoplasm with a large number of swollen vesicular nuclei on H and E staining. There was extensive variation of muscle fibre size. Large infiltrations of lymphocytes, plasma cells and macrophages were present in the interstitial connective tissue and around some veins. The arteries appeared normal. The connective tissue was mildly increased. The nerve endings were fragmented in the vicinity of degenerative muscle fibres. In the left seventh intercostal muscle and in the left sternocleidomastoideus muscle the described lesions above were less pronounced. In the left quadriceps femoris and gastrocnemius muscles the inflammatory reaction and the muscle fibre degeneration were less distinct, while in the left deltoid and biceps brachii muscles only discrete lesions were observed (Fig. 5). The left levator palpebrae superioris muscle was not affected.
Fig. 3. Paracrystalline inclusions with an internal periodicity of 21-23 nm are present, in the subsarcolemmic region. ;'; 39,000.
Fig. 4. Longitudinal section of the diaphragm. Most muscle fibres show waxy degeneration and lysis with invasion by lymphocytes, plasma cells and macrophages. Some basophylic fibres with swollen vesicular sarcolemmic nuclei are also present. The connective tissue is mildly increased. H and E; × 400.
458
Fig. 5. The degenerative changes and the inflammatory reaction are severe in the diaphragm (A), less pronounced in the sternocleidomastoid (B), moderate in the quadriceps femoris (C) and mild in 1he deltoideus muscle (D). H and E; "~ 160. DISCUSSION The clinical history a n d the biopsy and necropsy findings argue that the acute respiratory difficulties were due to a n acute polymyositis with p r e d o m i n a n t involvem e n t of the diaphragm. The pre-existing delayed developmental milestones in this
459 child can be related to the m a l f o r m a t i o n o f the central nervous system. R e s p i r a t o r y d i s o r d e r s occur in only 2 % of cases of polymyositis a n d even in a terminal stage o f m o r e generalized i n v o l v e m e n t they are extremely rare, unless a very acute myolytic process exists f r o m the start or a coexistent m a l i g n a n c y makes the muscular disease refractory to c o r t i c o s t e r o i d t h e r a p y (Pearson a n d Currie 1974). In the biopsy o f this case paracrystalline structures were found, which were similar to those described by C h o u a n d G u t m a n n (1970) a n d which were t h o u g h t to be Picorna virus-like particles. They were different f r o m other virus-like structures, such as the myxovirus-like structures ( C h o u 1968; F i d z i a n s k a 1973) a n d the filamentous inclusion bodies (Yunis a n d S a m a h a 1971). The aggression to the muscle fibres by activated l y m p h o c y t e s a n d m a c r o p h a g e s followed by disintegration o f the s a r c o l e m m a has been shown in polymyositis (Hughes a n d Esiri 1975), but is r e p o r t e d in cases o f t u r n o u t cells t r a n s p l a n t e d into striated muscle (Bab~i 1976). The histological a p p e a r a n c e o f the d i a p h r a g m in this case resembled the acute myolysis observed in muscles of the n e w b o r n infected by a Coxsackie virus ( F r e u d e n b e r g , R o u l e t a n d Nicole 1952), which is spread by the upper r e s p i r a t o r y tract. Coxsackie virus-like particles in muscles have been f o u n d in cases o f polymyositis ( M a s t a g l i a a n d W a l t o n 1970) a n d resemble " n a k e d " R N A Picorna viruses (Melnick, C o c k b u r n , Dallfdorf, G a r d , G e a r , M c H a m m o n , K a p l a n , Nagler, O k e r - B l o m , Rhodes, Sabin, Verlinde a n d von M a g n u s 1963). Polymyositis in which Picorna viruses are d e m o n s t r a t e d has a m o r e acute clinical course t h a n t h a t in which other virus-like particles ( C h o u 1973) are seen. A l t h o u g h no viral isolation h a d been p e r f o r m e d in the present case, there is some evidence to relate this p a r t i c u l a r muscular d i s o r d e r to an acute Coxsackie B2 virus infection.
REFERENCES Aicardi, J., D. Conti and E. Gouti6res (1974) Les formes n6onatales de la dystrophie myotonique de Steinert, J. neurol. Sci., 22:149 164. Babel, F. (1976) Etude ultrastructurale sur la pathog6nie du muscle stri6 par des tumeurs transplantables, J. Ultrastruet. Res., 56: 287-303. Barwick, D. D. and J. N. Walton (1963) Polymyositis, Amer. J. Med., 35:646 660. Bossen, E. H., J. D. Shelburne and B. S. Verkauf (1974) Respiratory muscle involvement in infantile myotonic dystrophy, Arch. Path., 97:250 252. Chou, S. M. (1968) Myxovirus-like structures and accompanying nuclear changes in chronic polymyositis, Areh. Path., 86: 649-658. Chou, S. M. (1973) Prospects of viral etiology in polymyositis. In: B. A. Kakulas (Ed.), Proceedings of the 2nd International Congress on Muscle Diseases, Perth, Australia, 1971, Part 2 (Clinical Studies hi Myology) (International Congress Series, No. 295), Excerpta Medica, Amsterdam, 1973, pp.
17-28. Chou, S. M. and L. Gutmann (1970) Picorna virus-like crystals in subacute polymyositis, Neurology (Minneap.), 20 : 205-213. De Reuck, J. and J. Willems (1975) Acute parathion poisoning - - Myopathic changes in the diaphragm, J. Neurol. (Berl.), 208: 309-314. De Reuck, J., C. Hooft, W. De Coster, H. Vanden Bossche and C. Cuvelier (1977) A progressive congenital myopathy - - Initial involvement of the diaphragm with Type I muscle fiber atrophy, Europ. Neurol., 15:217-226. Eaton, L. M. (1954) The perspective of neurology in regard to polymyositis, Neurology (Minneap.), 4 : 245-263.
460 Fidzianska, A. (1973) Virus-like structures in muscle in chronic polymyositis, Acta neuropath. ( Ber/. ,. 23: 23-31. Freudenherg, E., F. Roulet and R. Nicole (1952) Kongenitale Infection mit Coxsackie-Virus, Am~. paediat. (Basel), 178:150 161. Hughes, J. T. and M. M. Esiri (1975) Ultrastructural studies in human polymyositis, J. neurol. Sci.. 25 : 347-360. Mastaglia, F. L. and J. N. Walton (1970) Coxsackie virus-like particles in skeletal muscle from a case of polymyositis, J. neurol. Sci., 11 : 593-599. Melnick, J. L., W. C. Cockburn, G. Dalldorf, S. Gard, J. H. Gear, D. W. McHammon, M. M. Kaplan, F. P. Nagler, N. Oker-Blom, A. J. Rhodes, A. B. Sabin, J. D. Verlinde and H. Von Magnus (International Enterovirus Study Group) (1963) Picorna virus group, Virology, 19: 114-116. Pearson, C. M. and A. S. Rose (1960) Myositis ---The inflammatory disorders of muscle, Res. Publ. Ass. Res. Nerv. Ment. Dis., 38: 422~478. Pearson, C. M. and S. Currie (1974) Polymyositis and related disorders. In: J. N. Walton (Ed.), Disorders o f Voluntary Muscle, Churchill, Edinburgh, pp. 614-652. Walton, J. N. and R. D. Adams (1958) Polymyositis, Livingstone, Edinburgh. Yunis, E. J. and F. J. Samaha (1971) Inclusion body myositis, Lab. Invest., 25: 240-248.
