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Spinal muscular atrophy and hypertrophy of the calves
Journal of the Neurological Sciences, 1980, 44:275-279
275
© Elsevier/North-HollandBiomedicalPress
Sho~ Repo~
SPINAL MUSCULAR ATROPHY AND HYPERTROPHY OF THE CALVES G. BOUWSMAand G. K. VAN WIJNGAARDEN Rehabilitation Centre "De Trappenberg", Huizen and Department of Neurology, WilhelminaGasthuis, University of Amsterdam, Amsterdam, (The Netherlands)
(Received 14 August, 1979) (Accepted 11 September, 1979)
SUMMARY In 100 patients (59 males and 41 females) suffering from proximal spinal muscular atrophy, 23 presented with hypertrophy of the calves. These were all males. They all showed an elevation of serum CK-activity. The combination of spinal muscular atrophy, hypertrophy of the calves and elevated serum CK activity was not found in females.
INTRODUCTION Hypertrophy of the calf muscles often occurs in patients suffering from Duchenne muscular dystrophy. The occurrence of hypertrophic calves in benign spinal muscular atrophy is less known. Kugelberg and Welander (1956) described this symptom in two patients, and it was later reported by other authors, including Wiesendanger (1961), Archibald (1963), Tsukagoshi et al. (1966), Gardner-Medwin et al. (1967), Hetnarska et al. (1968), Peters et al. (1968), Namba et al. (1970), Van Wijngaarden and Bethlem (1973), Bundey and Lovelace (1975), Pearn and Hudgson (1978). It is still not clear whether one should regard the symptom as hypertrophy or pseudo-hypertrophy. Probably in the early stage there is true hypertrophy, as the calf muscle tries to compensate for the loss of function of the other weakened muscles. Children suffering from Duchenne's disease are able to contract the hypertrophic muscles well and the Achilles tendon reflexes persist for a long time, thereby denoting good muscle function. If the calf muscle tissue had been completely replaced by fat and connective tissue, good muscle function would be impossible. We therefore prefer to speak of hypertrophy. Apart from hypertrophy of the calf muscles hypertrophy of This studywas supported by a grant from the Prinses Beatrix Fonds.
276 other muscles has occasionally been reported (Gardner-Medwin et al. 1967; Hausmanowa-Petrucewicz et al. 1968). We investigated 100 patients presenting with proximal spinal muscular atrophy and we found hypertrophy of the calves in a rather large number of these patients. We assumed that hypertrophy of the calf existed if there was a distinct discrepancy between the bulk of the calf muscles and the other muscles of the limbs. MATERIAL AND METHODS Between January 1968 and July 1977, 103 patients were diagnosed as suffering from proximal spinal muscular atrophy at the Muscle Research Centre in Amsterdam. A neurological investigation was performed, as welt as determination of serum creatine kinase (CK) activity, electromyography of the left deltoid, right biceps brachii, right quadriceps femoris, left gastrocnemius and right extensor digitorum brevis muscles. The motor conduction velocity of the right peroneal nerve was measured. A muscle biopsy of the left quadriceps femoris muscle was investigated histologically and histochemically. The diagnosis of spinal muscular atrophy was made if a patient was suffering from progressive muscle weakness, together with signs of denervation whilst the motor conduction velocity of the peripheral nerves was normal (Van Wijngaarden and Bethlem 1973). Between April 1977 and September 1977 these patients were re-examined clinically and the serum CK activity was again determined. Twelve patients had meanwhile died. Of the 103 selected patients, 21 brothers and/or sisters proved to have muscle weakness, and had not yet been examined at the Muscle Research Centre. Nine of these 21 patients could subsequently be investigated. In total, 100 patients were involved in this investigation. RESULTS The 100 patients originated from 79 families. There were 59 males and 41 females varying in age between 1.5 and 61 years at the time of examination. The severity of the disease varied from very malignant to benign. There was no distinct border between the malignant and the benign types. The time of appearance of the disease varied from directly after birth until the age of 32 years. Twenty-three patients from 14 families presented with hypertrophic calves (Table 1). All these patients were male. They had all been able to walk, but in 8 of them this function had been lost. If several brothers in one family suffered from spinal muscular atrophy, they all had hypertrophic calves with the exception of two families. In families 12 and 13, four brothers suffered from spinal muscular atrophy. The 3 younger brothers presented with hypertrophic calves but the eldest brother no longer showed this sign. The two eldest brothers in these two families had been confined to wheelchairs for 11 and 6 years, respectively. In all 23 patients the serum CK activity was elevated (Table 1).
277 TABLE I CLINICAL AND BIOCHEMICAL CHARACTERISTICS OF MALES PRESENTING WITH HYPERTROPHIC CALVES Family
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Patient
E.J.H. W. de E. A.T. P.T. P.v.M. P.v.M. H.L T. de V. C.N. A.N. J.O. A.O. B.H. J.H. J.T. J.J.T. W.T. R.H. K.H. J.H. B.E. R.E. G.E.
Age (years)
CK act. a
First symptom
No longer able to walk from
Investigation
0-1 0-1 2 2 2 3 10 12 0-1 0-1 12 20 15 16 4 2 2 4 3 5 2 6 12
--10 -----8 7 ----18 22 24 --26 14 ---
9 9½ 18 27 32 22 39 31 10 12 22 25 27 29 23 26 30 18 27 29 15 20 23
200 85 341 280 531 473 152 583 1460 776 890 570 303 241 1200 530 455 771 848 408 960 912 1830
a Normal value < 50 E/I.
DISCUSSION F r o m this investigation the remarkable finding emerges that all the patients with spinal m u s c u l a r a t r o p h y a n d hypertrophic calves were males. I n the literature we f o u n d the c o m b i n a t i o n o f spinal m u s c u l a r a t r o p h y a n d hypertrophic calves in 45 reported cases (Table 2). The sex was stated in 34 cases as 24 males a n d 10 females. Pearo a n d H u d g s o n (1978) assumed that h y p e r t r o p h y of the calves would only appear i n those patients in w h o m the first symptoms manifested themselves after the first decade. This does n o t agree with our findings, n o r with those of H e t n a r s k a et al. (1968) or Peters et al. (1968). H y p e r t r o p h y of the calves is n o t usually seen i n very y o u n g children. The age at which we f o u n d h y p e r t r o p h y o f the calves varied from 9 to 39 years (Table 1) a n d this agrees with the findings o f other authors (Table 2). It is very p r o b a b l e that calf h y p e r t r o p h y disappears after p r o l o n g e d immobility. The eldest two patients of families 12 a n d 13 who h a d been confined to wheelchairs for a long time had n o calf hypertrophy, whereas the y o u n g e r brothers did.
278 TABLE 2 REVIEW OF THE LITERATURE ON PATIENTS WITH SPINAL M U S C U L A R ATROPHY PRESENTING WITH HYPERTROPHIC CALVES Year
Author(s)
Sex
Age last examined
First symptom
CK activity
1956
Kugelberg and Welander
1961 1963
Wiesendanger Archibald
1966
Tsukagoshi eta!.
1967 1968
Gardner-Medwin et al. Hetnarska et al.
1968
Peters et al.
1970 1973
Namba et al. Van Wijngaarden and Bethlem
1975 1978
Bundey and Lovelace Pearn and Hudgson
f 57 17 -m 24 14 -5 patients with calf hypertrophy m 21 2 -m 23 11 -f 64 14 n m 38 16 27.7 (n: < 20) m 33 15 n m 8 1 21 (n: < 2) f 14 1 4.6 f 18 10 4.9 m 33 17 18.2 f 31 6 n m 21 1 68 f 13 1 2.2 m 19 2 8.0 f 19 2 7.2 f 11 3 n m 11 8 n m 13 6 9.2 m 17 6 5.0 m 20 12 24.3 m 25 5 - - (n : < 2.9) m 14 6 5.4 f 16 7 7.2 m 28 < 1 m 13 2-5 806 (n: < 50) m 9 1 528 m 24 1 308 m 18 2-5 891 6 patients out of 50 patients presented hypertrophic calves f 43 16 -m 23 11 -m 24 14 -m 17 14 -m 33 _]:20
T h e s e r u m C K a c t i v i t y w a s e l e v a t e d i n all o f o u r p a t i e n t s , a n d c o m p l e m e n t s t h e f i n d i n g s o f H e t n a r s k a e t al. (1968) a n d V a n W i j n g a a r d e n a n d B e t h l e m (1973). ACKNOWLEDGEMENTS W e w a n t t o e x p r e s s o u r g r a t i t u d e t o P r o f . J. B e t h l e m , M . D . , h e a d o f t h e M u s c l e R e s e a r c h C e n t r e i n A m s t e r d a m , w h e r e t h i s s t u d y w a s m a d e a n d t o A. V a n W i e r i n g e n M . D . for supervising the English text.
279 REFERENCES Archibald, K. C. (1973) Problems in diagnosing progressive muscular and neuromuscular diseases, Arch. phys. Med. Rehab., 44: 353-359. Bundey, S. and R. E. Lovelace (1975) A clinical and genetic study of chronic proximal spinal muscular atrophy, Brain, 98: 455-472. Gardner-Medwin, D., P. Hudgson and J. N. Walton (1967) Benign spinal muscular atrophy arising in childhood and adolescence, J. neurol, Sci., 5: 121-158. Hausmanowa-Petrucewicz, I., V. Askanas, B. Badurska, B. Emeryk, A. Fidzianska, W. Garbalinska, L. Hetnarska, H. Jedrzejowska, Z. Kamieniecka, I. Niebr6j-Dobosz, J. Prot and E. Sawicka (1968) Infantile and juvenile spinal muscular atrophy, J. neurol. Sci., 6: 269-287. Hetnarska, L., J. Prot and E. Sawicka (1968) Creatine phosphokinase activity in spinal muscular atrophy, J. neurol. Sci., 6: 261-267. Kugelberg, E. and L. Welander (1956) Heredofamilial juvenile muscular atrophy simulating muscular dystrophy, Arch. Neurol. Psychiat. (Chic.), 75 : 500-509. Namba, T., D. C. Aberfeld and D. Grob (1970) Chronic spinal muscular atrophy, J. neurol. Sci., 11 : 401-423. Pearn, J. and P. Hudgson (1978) Anterior-horn cell degeneration and gross calf hypertrophy with adolescent onset, Lancet, 2: 1059-1061. Peters, H. A., J. M. Opitz, I. Goto and H. H. Reese (1968) The benign proximal spinal progressive muscular atrophies, Acta neurol, scand., 44: 542-560. Tsukagoshi, H., H. Sugita, T. Furukawa, T. Tsubaki and E. Ono (1966) Kugelberg-Welander syndrome with dominant inheritance, Arch. NeuroL (Chic.), 14: 378-381. Wiesendanger, M. (1961) Uber einen Stammbaum mit Dystrophie-~ihnlicher spinaler Muskelatrophie, Psych. Neurol. Neurochir.. 69: 224-233. Van Wijngaarden, G. K and J. Bethlem (1973) Benign infantile spinal muscular atrophy, Brain, 96: 163-170.
275
© Elsevier/North-HollandBiomedicalPress
Sho~ Repo~
SPINAL MUSCULAR ATROPHY AND HYPERTROPHY OF THE CALVES G. BOUWSMAand G. K. VAN WIJNGAARDEN Rehabilitation Centre "De Trappenberg", Huizen and Department of Neurology, WilhelminaGasthuis, University of Amsterdam, Amsterdam, (The Netherlands)
(Received 14 August, 1979) (Accepted 11 September, 1979)
SUMMARY In 100 patients (59 males and 41 females) suffering from proximal spinal muscular atrophy, 23 presented with hypertrophy of the calves. These were all males. They all showed an elevation of serum CK-activity. The combination of spinal muscular atrophy, hypertrophy of the calves and elevated serum CK activity was not found in females.
INTRODUCTION Hypertrophy of the calf muscles often occurs in patients suffering from Duchenne muscular dystrophy. The occurrence of hypertrophic calves in benign spinal muscular atrophy is less known. Kugelberg and Welander (1956) described this symptom in two patients, and it was later reported by other authors, including Wiesendanger (1961), Archibald (1963), Tsukagoshi et al. (1966), Gardner-Medwin et al. (1967), Hetnarska et al. (1968), Peters et al. (1968), Namba et al. (1970), Van Wijngaarden and Bethlem (1973), Bundey and Lovelace (1975), Pearn and Hudgson (1978). It is still not clear whether one should regard the symptom as hypertrophy or pseudo-hypertrophy. Probably in the early stage there is true hypertrophy, as the calf muscle tries to compensate for the loss of function of the other weakened muscles. Children suffering from Duchenne's disease are able to contract the hypertrophic muscles well and the Achilles tendon reflexes persist for a long time, thereby denoting good muscle function. If the calf muscle tissue had been completely replaced by fat and connective tissue, good muscle function would be impossible. We therefore prefer to speak of hypertrophy. Apart from hypertrophy of the calf muscles hypertrophy of This studywas supported by a grant from the Prinses Beatrix Fonds.
276 other muscles has occasionally been reported (Gardner-Medwin et al. 1967; Hausmanowa-Petrucewicz et al. 1968). We investigated 100 patients presenting with proximal spinal muscular atrophy and we found hypertrophy of the calves in a rather large number of these patients. We assumed that hypertrophy of the calf existed if there was a distinct discrepancy between the bulk of the calf muscles and the other muscles of the limbs. MATERIAL AND METHODS Between January 1968 and July 1977, 103 patients were diagnosed as suffering from proximal spinal muscular atrophy at the Muscle Research Centre in Amsterdam. A neurological investigation was performed, as welt as determination of serum creatine kinase (CK) activity, electromyography of the left deltoid, right biceps brachii, right quadriceps femoris, left gastrocnemius and right extensor digitorum brevis muscles. The motor conduction velocity of the right peroneal nerve was measured. A muscle biopsy of the left quadriceps femoris muscle was investigated histologically and histochemically. The diagnosis of spinal muscular atrophy was made if a patient was suffering from progressive muscle weakness, together with signs of denervation whilst the motor conduction velocity of the peripheral nerves was normal (Van Wijngaarden and Bethlem 1973). Between April 1977 and September 1977 these patients were re-examined clinically and the serum CK activity was again determined. Twelve patients had meanwhile died. Of the 103 selected patients, 21 brothers and/or sisters proved to have muscle weakness, and had not yet been examined at the Muscle Research Centre. Nine of these 21 patients could subsequently be investigated. In total, 100 patients were involved in this investigation. RESULTS The 100 patients originated from 79 families. There were 59 males and 41 females varying in age between 1.5 and 61 years at the time of examination. The severity of the disease varied from very malignant to benign. There was no distinct border between the malignant and the benign types. The time of appearance of the disease varied from directly after birth until the age of 32 years. Twenty-three patients from 14 families presented with hypertrophic calves (Table 1). All these patients were male. They had all been able to walk, but in 8 of them this function had been lost. If several brothers in one family suffered from spinal muscular atrophy, they all had hypertrophic calves with the exception of two families. In families 12 and 13, four brothers suffered from spinal muscular atrophy. The 3 younger brothers presented with hypertrophic calves but the eldest brother no longer showed this sign. The two eldest brothers in these two families had been confined to wheelchairs for 11 and 6 years, respectively. In all 23 patients the serum CK activity was elevated (Table 1).
277 TABLE I CLINICAL AND BIOCHEMICAL CHARACTERISTICS OF MALES PRESENTING WITH HYPERTROPHIC CALVES Family
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Patient
E.J.H. W. de E. A.T. P.T. P.v.M. P.v.M. H.L T. de V. C.N. A.N. J.O. A.O. B.H. J.H. J.T. J.J.T. W.T. R.H. K.H. J.H. B.E. R.E. G.E.
Age (years)
CK act. a
First symptom
No longer able to walk from
Investigation
0-1 0-1 2 2 2 3 10 12 0-1 0-1 12 20 15 16 4 2 2 4 3 5 2 6 12
--10 -----8 7 ----18 22 24 --26 14 ---
9 9½ 18 27 32 22 39 31 10 12 22 25 27 29 23 26 30 18 27 29 15 20 23
200 85 341 280 531 473 152 583 1460 776 890 570 303 241 1200 530 455 771 848 408 960 912 1830
a Normal value < 50 E/I.
DISCUSSION F r o m this investigation the remarkable finding emerges that all the patients with spinal m u s c u l a r a t r o p h y a n d hypertrophic calves were males. I n the literature we f o u n d the c o m b i n a t i o n o f spinal m u s c u l a r a t r o p h y a n d hypertrophic calves in 45 reported cases (Table 2). The sex was stated in 34 cases as 24 males a n d 10 females. Pearo a n d H u d g s o n (1978) assumed that h y p e r t r o p h y of the calves would only appear i n those patients in w h o m the first symptoms manifested themselves after the first decade. This does n o t agree with our findings, n o r with those of H e t n a r s k a et al. (1968) or Peters et al. (1968). H y p e r t r o p h y of the calves is n o t usually seen i n very y o u n g children. The age at which we f o u n d h y p e r t r o p h y o f the calves varied from 9 to 39 years (Table 1) a n d this agrees with the findings o f other authors (Table 2). It is very p r o b a b l e that calf h y p e r t r o p h y disappears after p r o l o n g e d immobility. The eldest two patients of families 12 a n d 13 who h a d been confined to wheelchairs for a long time had n o calf hypertrophy, whereas the y o u n g e r brothers did.
278 TABLE 2 REVIEW OF THE LITERATURE ON PATIENTS WITH SPINAL M U S C U L A R ATROPHY PRESENTING WITH HYPERTROPHIC CALVES Year
Author(s)
Sex
Age last examined
First symptom
CK activity
1956
Kugelberg and Welander
1961 1963
Wiesendanger Archibald
1966
Tsukagoshi eta!.
1967 1968
Gardner-Medwin et al. Hetnarska et al.
1968
Peters et al.
1970 1973
Namba et al. Van Wijngaarden and Bethlem
1975 1978
Bundey and Lovelace Pearn and Hudgson
f 57 17 -m 24 14 -5 patients with calf hypertrophy m 21 2 -m 23 11 -f 64 14 n m 38 16 27.7 (n: < 20) m 33 15 n m 8 1 21 (n: < 2) f 14 1 4.6 f 18 10 4.9 m 33 17 18.2 f 31 6 n m 21 1 68 f 13 1 2.2 m 19 2 8.0 f 19 2 7.2 f 11 3 n m 11 8 n m 13 6 9.2 m 17 6 5.0 m 20 12 24.3 m 25 5 - - (n : < 2.9) m 14 6 5.4 f 16 7 7.2 m 28 < 1 m 13 2-5 806 (n: < 50) m 9 1 528 m 24 1 308 m 18 2-5 891 6 patients out of 50 patients presented hypertrophic calves f 43 16 -m 23 11 -m 24 14 -m 17 14 -m 33 _]:20
T h e s e r u m C K a c t i v i t y w a s e l e v a t e d i n all o f o u r p a t i e n t s , a n d c o m p l e m e n t s t h e f i n d i n g s o f H e t n a r s k a e t al. (1968) a n d V a n W i j n g a a r d e n a n d B e t h l e m (1973). ACKNOWLEDGEMENTS W e w a n t t o e x p r e s s o u r g r a t i t u d e t o P r o f . J. B e t h l e m , M . D . , h e a d o f t h e M u s c l e R e s e a r c h C e n t r e i n A m s t e r d a m , w h e r e t h i s s t u d y w a s m a d e a n d t o A. V a n W i e r i n g e n M . D . for supervising the English text.
279 REFERENCES Archibald, K. C. (1973) Problems in diagnosing progressive muscular and neuromuscular diseases, Arch. phys. Med. Rehab., 44: 353-359. Bundey, S. and R. E. Lovelace (1975) A clinical and genetic study of chronic proximal spinal muscular atrophy, Brain, 98: 455-472. Gardner-Medwin, D., P. Hudgson and J. N. Walton (1967) Benign spinal muscular atrophy arising in childhood and adolescence, J. neurol, Sci., 5: 121-158. Hausmanowa-Petrucewicz, I., V. Askanas, B. Badurska, B. Emeryk, A. Fidzianska, W. Garbalinska, L. Hetnarska, H. Jedrzejowska, Z. Kamieniecka, I. Niebr6j-Dobosz, J. Prot and E. Sawicka (1968) Infantile and juvenile spinal muscular atrophy, J. neurol. Sci., 6: 269-287. Hetnarska, L., J. Prot and E. Sawicka (1968) Creatine phosphokinase activity in spinal muscular atrophy, J. neurol. Sci., 6: 261-267. Kugelberg, E. and L. Welander (1956) Heredofamilial juvenile muscular atrophy simulating muscular dystrophy, Arch. Neurol. Psychiat. (Chic.), 75 : 500-509. Namba, T., D. C. Aberfeld and D. Grob (1970) Chronic spinal muscular atrophy, J. neurol. Sci., 11 : 401-423. Pearn, J. and P. Hudgson (1978) Anterior-horn cell degeneration and gross calf hypertrophy with adolescent onset, Lancet, 2: 1059-1061. Peters, H. A., J. M. Opitz, I. Goto and H. H. Reese (1968) The benign proximal spinal progressive muscular atrophies, Acta neurol, scand., 44: 542-560. Tsukagoshi, H., H. Sugita, T. Furukawa, T. Tsubaki and E. Ono (1966) Kugelberg-Welander syndrome with dominant inheritance, Arch. NeuroL (Chic.), 14: 378-381. Wiesendanger, M. (1961) Uber einen Stammbaum mit Dystrophie-~ihnlicher spinaler Muskelatrophie, Psych. Neurol. Neurochir.. 69: 224-233. Van Wijngaarden, G. K and J. Bethlem (1973) Benign infantile spinal muscular atrophy, Brain, 96: 163-170.