Diferenciação precoce entre distrofia muscular de duchenne e de becker estudo clínico, laboratorial, eletrofisiológico, histoquímico e imuno-histoquímico de 138 casos: clinical, laboratory, electrophysiologic, histochemical and immunohistochemical study of 138 cases

Werneck, Lineu C.; Ferraz, Leila E.; Scola, Rosana H.

doi:10.1590/S0004-282X1992000400009

Resumos

Foram estudados por análise estatística 194 parâmetros clínicos, laboratoriais, eletrofisiológicos, histoquímicos e imuno-histoquímicos de 112 casos de distrofia muscular de Duchenne (DMD) e de 26 casos de distrofia muscular de Becker (DMB). Houve diferença significante (p < 0,05) entre as duas doenças com respeito a época de início de diversos sintomas, dados do exame neurológico e alterações específicas na biópsia muscular. A biópsia muscular (BM) isolada foi diagnóstica em 52,7% dos casos de DMD e em 69,2% dos de DMB. Por imunofluorescência (60 casos) a distrofina estava ausente em 87% dos casos de DMD e apresentava falhas focais em todos os casos de DMB. A BM foi concordante com a imunofluorescência para distrofina em 82,6% dos casos de DMD e 71,4% dos de DMB. São feitos comentários a respeito dos dados encontrados e os da literatura, bem como sobre a dificuldade diagnóstica para diferenciação precoce das duas entidades.

Distrofia muscular de Duchenne e de Becker; diferenciação precoce; análise estatística de dados (clínicos, laboratoriais, eletromiográficos, histoquímicos, imuno-histoquímicos)

194 clinical, laboratory, electrophysiologic, histological, histochemical and immunohistochemical parameters "were studied through statistical analysis in 112 cases of Duchenne muscular dystrophy (DMD) and in 26 cases of Becker muscular dystrophy (BMD). It was found a significant statistical difference. (p<0.05) between the two groups concerning the age of evaluation, beginning of symptoms, difficulty in walking, running, climbing and going downstairs, frequent falling down, support to walk, localized muscle pain, stopping climb stairs, and inability to walk. Muscle biopsy showed statistically significant (p<0.05) differences between the two groups regarding the intensity of connective tissue and focal adipose tissue proliferation, presence of diffuse rounded atrophic and angulated fibers, diffuse hypertrophic and splitting fibers. There were also differences regarding excessive internal fibers nuclei, hypertrophic types 1 and 2 fibers, angulated atrophic fibers and focal increasing in the NADH-TR, angulated atrophic fibers in non-specific esterase, and accumulated NBT in the periphery of fibers in succinic dehidrogenase. Isolatedly muscle biopsy gave the correct diagnosis in 52.7% of DMD cases and in 69.2%. of BMD cases. Dystrophin detection by immunofluorescence (60 cases) showed: absence in 87.0% of fibers in DMD cases, and sarcolemmial membrane discontinuités in all BMD¹ cases. The muscle biopsy diagnosis had an agreement with the dystrophin results in 82.6% of DMD¹ cases and 71.4% of BMD cases.

Duchenne and Becker muscular dystrophy; early diagnostic differentiation; statistical analysis of data (clinical, laboratory, electromyographic, histochemical, immunohistochemical)

Diferenciação precoce entre distrofia muscular de duchenne e de becker estudo clínico, laboratorial, eletrofisiológico, histoquímico e imuno-histoquímico de 138 casos

Early differentiation between Duchenne and Becker muscular dystrophy: clinical, laboratory, electrophysiologic, histochemical and immunohistochemical study of 138 cases

Lineu C. Werneck^I; Leila E. Ferraz^II; Rosana H. Scola^III

^IProfessor Titular de Clínica Médica (Neurologia). Estudo realizado no Serviço de Doenças Neuromusculares do Hospital de Clínicas e Especialidade de Neurologia do Departamento de Clínica Médica da Universidade Federal do Paraná (UFPR), Curitiba

^IINeurologista e Mes-tranda de Medicina Interna. Estudo realizado no Serviço de Doenças Neuromusculares do Hospital de Clínicas e Especialidade de Neurologia do Departamento de Clínica Médica da Universidade Federal do Paraná (UFPR), Curitiba

^IIINeurofisiologista Clínica e Mestranda de Medicina Interna. Estudo realizado no Serviço de Doenças Neuromusculares do Hospital de Clínicas e Especialidade de Neurologia do Departamento de Clínica Médica da Universidade Federal do Paraná (UFPR), Curitiba

RESUMO

Foram estudados por análise estatística 194 parâmetros clínicos, laboratoriais, eletrofisiológicos, histoquímicos e imuno-histoquímicos de 112 casos de distrofia muscular de Duchenne (DMD) e de 26 casos de distrofia muscular de Becker (DMB). Houve diferença significante (p < 0,05) entre as duas doenças com respeito a época de início de diversos sintomas, dados do exame neurológico e alterações específicas na biópsia muscular. A biópsia muscular (BM) isolada foi diagnóstica em 52,7% dos casos de DMD e em 69,2% dos de DMB. Por imunofluorescência (60 casos) a distrofina estava ausente em 87% dos casos de DMD e apresentava falhas focais em todos os casos de DMB. A BM foi concordante com a imunofluorescência para distrofina em 82,6% dos casos de DMD e 71,4% dos de DMB. São feitos comentários a respeito dos dados encontrados e os da literatura, bem como sobre a dificuldade diagnóstica para diferenciação precoce das duas entidades.

Palavras-chave: Distrofia muscular de Duchenne e de Becker, diferenciação precoce, análise estatística de dados (clínicos, laboratoriais, eletromiográficos, histoquímicos, imuno-histoquímicos).

SUMMARY

194 clinical, laboratory, electrophysiologic, histological, histochemical and immunohistochemical parameters "were studied through statistical analysis in 112 cases of Duchenne muscular dystrophy (DMD) and in 26 cases of Becker muscular dystrophy (BMD). It was found a significant statistical difference. (p<0.05) between the two groups concerning the age of evaluation, beginning of symptoms, difficulty in walking, running, climbing and going downstairs, frequent falling down, support to walk, localized muscle pain, stopping climb stairs, and inability to walk. Muscle biopsy showed statistically significant (p<0.05) differences between the two groups regarding the intensity of connective tissue and focal adipose tissue proliferation, presence of diffuse rounded atrophic and angulated fibers, diffuse hypertrophic and splitting fibers. There were also differences regarding excessive internal fibers nuclei, hypertrophic types 1 and 2 fibers, angulated atrophic fibers and focal increasing in the NADH-TR, angulated atrophic fibers in non-specific esterase, and accumulated NBT in the periphery of fibers in succinic dehidrogenase. Isolatedly muscle biopsy gave the correct diagnosis in 52.7% of DMD cases and in 69.2%. of BMD cases. Dystrophin detection by immunofluorescence (60 cases) showed: absence in 87.0% of fibers in DMD cases, and sarcolemmial membrane discontinuités in all BMD¹ cases. The muscle biopsy diagnosis had an agreement with the dystrophin results in 82.6% of DMD¹ cases and 71.4% of BMD cases.

Key words: Duchenne and Becker muscular dystrophy, early diagnostic differentiation, statistical analysis of data (clinical, laboratory, electromyographic, histochemical, immunohistochemical).

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Agradecimento Agradecemos a Srta. Sumico Nakagawa pela assistência técnica nas preparações histológicas e nas imunofluorescências.

Suporte parcial pelo CNPq, processo 820224/88-0.

Dr. Lineu César Werneck Rua Ewaldo Schiebler 780 - 82500 Curitiba PR - Brasil.

1. Baunbach LL, Chamberlain P, Ward PA, Farwell NJ, Caskey CT. Molecular and clinical correlations of deletions leading to Duchenne and Becker muscular dystrophies. Neurology 1989, 39:465-474.
2. Bonilla E, Samitt CE, Miranda AF, Hays AP, Salviat G, DiMauro S, Kunkel L, Hoffman BP, Rowland LP. Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell 1988, 54:447-452.
3. Bradley WG, Jones MZ, Mussini JM, Fawcet PRW. Becker-type muscular dystrophy. Muscle & Nerve 1978, 1:111-132.
4. Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Miller JP, Provice MA, Cidd Group. Clinical investigation in Duchenne dystrophy: 2. Determination of the «power» of therapeutic trials based on the natural history. Muscle & Nerve 1983, 6:91-103.
5. Brooke MN, Griggs RC, Mendell JR, Fenichel GM, Shumate JB, Pellegrino RJ. Clinical trial in Duchenne dystrophy: I. The design of the protocol. Muscle & Nerve 1981, 4 :186-197.
6. DeSilva S, Drachman DB, Mellits D, Kunel RW. Prednisone treatment in Duchenne muscular dystrophy. Arch Neurol 1987, 44 :818-822.
7. Forrest SM, Cross CS, Speer A, Gardner-Medwin C, Burn J, Davies KB. Preferencial deletion of axons in Duchenne and Becker muscular dystrophies. Nature 1987, 329:638-639.
8. Grimm T. Becker dystrophy. In Engel AG, Banker BQ (eds) : Myology. New York: McGraw-Hill, 1986.
9. Gutmann DH, Fischbeck KH. Molecular biology of Duchenne and Becker muscular dystrophy: clinical aplications Ann Neurol 1989, 26:189-194.
10. Hart KA, Hodgson S, Walker A, Cole CG, Johnson L, Dubowitz V, Bobrow M. DNA deletion in mild and severe Becker muscular dystrophy. Hum Genet 1987, 75:281-285.
11. Hoffmann EP, Brown RHJr, Hunkel LH. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987, 51:919-928.
12. Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Watterston R, Brooke M, Specht L, Kupsky W, Chamberlain J, Caskey T, Shapiro F, Kunkel LM. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N Engl J Med 1988, 318:1363-1368.
13. Hofmann EP, Hudecki MS, Rosenberg PA, Polina CM, Kunkel LM. Cell and fiber-type distribution of dystrophin. Neuron 1988, 1:411-420.
14. Hoffman EP, Knudson CM, Campbell KP, Kunkel LH, Subcellular fraction of dystrophin to the triads of the skeletal muscle. Nature 1987, 330:754-758.
15. Koening M, Hoffman EP, Bertelson CJ, Monaco AF, Feener C, Kunkel LH. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 1987, 50:509-517.
16. Mabry CC, Roeckel IE, Munich RL, Robertson D. X-linked pseudohypertrophic muscular dystrophy with a late onset and slow progression. N Engl J Med 1965, 27 3:1062-1070.
17. Markand ON, North RR, D'Agostinho AN, Daly DD. Benign sex-linked muscular dystrophy. Neurology 1969, 19:617-633.
18. Medori R, Brooke MH, Waterston H. Genetic abnormalities in Duchenne and Becker dystrophies: clinical correlations. Neurology 1989, 39:461-465.
19. Monaco AP, Neve RL, Colleti-Feener C, Bertelson CJ, Kurnit DM, Kunkel LH. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 1986, 323:646-650.
20. Ringel SP, Carrol JE, Schold SC. The spectrum of mild X-linked recessive muscular dystrophy. Arch Neurol 1977, 34:408-416.
21. Shaw RF, Dreifus FE. Mild and severe forms of X-linked muscular dystrophy. Arch Neurol 1969, 20:451-460.
22. Shaw RF, Markand ON, North RR, D'Agostino AN, Daly DD. Benign sex-linked muscular dystrophy. Neurology 1969, 19:617-633.
23. Walton JN, Gardner-Medwin D. Progressive muscular dystrophy and the myotonic disorders. In Walton JN: Disorders of Voluntary Muscle. Edinburg: Churchill Livingstone, 1981.
24. Werneck LC. O valor da biópsia muscular em neurologia. Rev. Bras. Clin Terap 1981, 10 (edição especial) : 2-22.
25. Werneck LC, Bonilla E. Distrofina na diferenciação das distrofias de Duchenne e Becker: estudo imuno-histoquímico comparado com o estadio clínico, enzimas séricas e biópsia muscular. Arq Neuro-Psiquiat (Sao Paulo) 1990, 48:454-464.
26. Werneck LC, Lima JGC, Koehler H. Correlation between specific histological and electromyographic findings in neuromuscular disorders. Arq Neuro-Psiquiat (São Paulo) 1988, 46:264-271.
27. Zellweger H, Hanson JW. Slowly progressive X-linked recessive muscular dystrophy (Type IHb). Arch Intern Med 1967, 120:525-535.

Datas de Publicação

Publicação nesta coleção
22 Fev 2011
Data do Fascículo
Dez 1992

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Baunbach LL, Chamberlain P, Ward PA, Farwell NJ, Caskey CT. Molecular and clinical correlations of deletions leading to Duchenne and Becker muscular dystrophies. Neurology 1989, 39:465-474.

[2] 2. Bonilla E, Samitt CE, Miranda AF, Hays AP, Salviat G, DiMauro S, Kunkel L, Hoffman BP, Rowland LP. Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell 1988, 54:447-452.

[3] 3. Bradley WG, Jones MZ, Mussini JM, Fawcet PRW. Becker-type muscular dystrophy. Muscle & Nerve 1978, 1:111-132.

[4] 4. Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Miller JP, Provice MA, Cidd Group. Clinical investigation in Duchenne dystrophy: 2. Determination of the «power» of therapeutic trials based on the natural history. Muscle & Nerve 1983, 6:91-103.

[5] 5. Brooke MN, Griggs RC, Mendell JR, Fenichel GM, Shumate JB, Pellegrino RJ. Clinical trial in Duchenne dystrophy: I. The design of the protocol. Muscle & Nerve 1981, 4 :186-197.

[6] 6. DeSilva S, Drachman DB, Mellits D, Kunel RW. Prednisone treatment in Duchenne muscular dystrophy. Arch Neurol 1987, 44 :818-822.

[7] 7. Forrest SM, Cross CS, Speer A, Gardner-Medwin C, Burn J, Davies KB. Preferencial deletion of axons in Duchenne and Becker muscular dystrophies. Nature 1987, 329:638-639.

[8] 8. Grimm T. Becker dystrophy. In Engel AG, Banker BQ (eds) : Myology. New York: McGraw-Hill, 1986.

[9] 9. Gutmann DH, Fischbeck KH. Molecular biology of Duchenne and Becker muscular dystrophy: clinical aplications Ann Neurol 1989, 26:189-194.

[10] 10. Hart KA, Hodgson S, Walker A, Cole CG, Johnson L, Dubowitz V, Bobrow M. DNA deletion in mild and severe Becker muscular dystrophy. Hum Genet 1987, 75:281-285.

[11] 11. Hoffmann EP, Brown RHJr, Hunkel LH. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987, 51:919-928.

[12] 12. Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Watterston R, Brooke M, Specht L, Kupsky W, Chamberlain J, Caskey T, Shapiro F, Kunkel LM. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N Engl J Med 1988, 318:1363-1368.

[13] 13. Hofmann EP, Hudecki MS, Rosenberg PA, Polina CM, Kunkel LM. Cell and fiber-type distribution of dystrophin. Neuron 1988, 1:411-420.

[14] 14. Hoffman EP, Knudson CM, Campbell KP, Kunkel LH, Subcellular fraction of dystrophin to the triads of the skeletal muscle. Nature 1987, 330:754-758.

[15] 15. Koening M, Hoffman EP, Bertelson CJ, Monaco AF, Feener C, Kunkel LH. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 1987, 50:509-517.

[16] 16. Mabry CC, Roeckel IE, Munich RL, Robertson D. X-linked pseudohypertrophic muscular dystrophy with a late onset and slow progression. N Engl J Med 1965, 27 3:1062-1070.

[17] 17. Markand ON, North RR, D'Agostinho AN, Daly DD. Benign sex-linked muscular dystrophy. Neurology 1969, 19:617-633.

[18] 18. Medori R, Brooke MH, Waterston H. Genetic abnormalities in Duchenne and Becker dystrophies: clinical correlations. Neurology 1989, 39:461-465.

[19] 19. Monaco AP, Neve RL, Colleti-Feener C, Bertelson CJ, Kurnit DM, Kunkel LH. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 1986, 323:646-650.

[20] 20. Ringel SP, Carrol JE, Schold SC. The spectrum of mild X-linked recessive muscular dystrophy. Arch Neurol 1977, 34:408-416.

[21] 21. Shaw RF, Dreifus FE. Mild and severe forms of X-linked muscular dystrophy. Arch Neurol 1969, 20:451-460.

[22] 22. Shaw RF, Markand ON, North RR, D'Agostino AN, Daly DD. Benign sex-linked muscular dystrophy. Neurology 1969, 19:617-633.

[23] 23. Walton JN, Gardner-Medwin D. Progressive muscular dystrophy and the myotonic disorders. In Walton JN: Disorders of Voluntary Muscle. Edinburg: Churchill Livingstone, 1981.

[24] 24. Werneck LC. O valor da biópsia muscular em neurologia. Rev. Bras. Clin Terap 1981, 10 (edição especial) : 2-22.

[25] 25. Werneck LC, Bonilla E. Distrofina na diferenciação das distrofias de Duchenne e Becker: estudo imuno-histoquímico comparado com o estadio clínico, enzimas séricas e biópsia muscular. Arq Neuro-Psiquiat (Sao Paulo) 1990, 48:454-464.

[26] 26. Werneck LC, Lima JGC, Koehler H. Correlation between specific histological and electromyographic findings in neuromuscular disorders. Arq Neuro-Psiquiat (São Paulo) 1988, 46:264-271.

[27] 27. Zellweger H, Hanson JW. Slowly progressive X-linked recessive muscular dystrophy (Type IHb). Arch Intern Med 1967, 120:525-535.