Paralisia periódica: estudo anátomo-patológico do músculo esquelético de 14 pacientes

Tengan, Célia Harumi; Oliveira, Acary Souza Bulle; Morita, Maria da Penha Ananias; Kiyomoto, Beatriz Hitomi; Schmidt, Beny; Gabbai, Alberto Alain

doi:10.1590/S0004-282X1994000100006

Resumos

A paralisia periódica é entidade caracterizada por crises de fraqueza muscular relacionadas com alterações do nível sérico de potássio. A biópsia muscular pode mostrar alterações específicas ou inespecíficas. Nosso estudo tem como objetivo a análise de 17 biópsias musculares de 14 pacientes com paralisia periódica (14 hipocalêmica, 2 hipercalêmica). Todas as biópsias mostraram alguma alteração histopatológica. Quatorze biópsias apresentavam vacúolos, que se caracterizavam por serem únicos, de localização periférica, de aparecimento frequente e preferentemente em fibras do tipo I. Os vacúolos eram mais visualizados naqueles pacientes com longa evolução e sem relação com a frequência de crises. Os agregados tubulares foram encontrados em 10 biópsias principalmente naqueles pacientes com crises frequentes e doença de longa evolução. Em 3 pacientes foram realizadas 2 biópsias, notando-se piora das alterações em 2. Um paciente evoluiu com quadro clínico de miopatia permanente, confirmado pela biópsia muscular. Alterações inespecíficas foram encontradas em graus variáveis em 15 biópsias. Nosso estudo mostra que os vacúolos e os agregados tubulares são achados frequentes na paralisia periódica, constituindo importante auxílio diagnóstico. Alterações miopáticas evidentes à biópsia sugerem o aparecimento de miopatia permanente, quadro decorrente de doença de longa evolução ou crises severas.

paralisia periódica; biópsia; músculo esquelético; histotogia; vacúolos; agregados tubulares

Periodic paralysis is a rare disease, characterized by transient weakness associated with abnormal levels of serum potassium. Muscle biopsy may show a wide range of abnormalities, vacuoles being more specifically linked to the disease. We analysed 17 muscle biopsies from 14 patients with periodic paralysis (14 hypokalemic, 2 hyperkalemic). All of them showed at least one histological abnormality. Fourteen specimens showed vacuoles that were peripheral, single, frequent and preferentially found in type I fibers. Frequency or severity of attacks did not correlate with the presence of vacuoles but those were more easily found in patients with long term disease. Ten biopsies showed tubular aggregates, specially on the patients with frequent crises or long term disease. A second biopsy was done in three patients and in two we observed a worsening of the histopathologic picture. One patient manifested interictal weakness with evident myopathic changes on the muscle biopsy. Nonspecific changes were found in variable degrees in 15 biopsies. Our study shows that vacuoles and tubular aggregates are frequent changes in periodic paralysis and therefore helpful for the diagnosis. Important myopathic findings in the muscle biopsy suggest a permanent myopathy which probably develops after severe crises or long term disease.

periodic paralysis; biopsy; skeletal muscle; vacuoles; tubular aggregates

Paralisia periódica: estudo anátomo-patológico do músculo esquelético de 14 pacientes

Periodic paralysis: anatomo-pathology of skeletal muscle of 14 patients

Célia Harumi Tengan^I; Acary Souza Bulle Oliveira^I; Maria da Penha Ananias Morita^I; Beatriz Hitomi Kiyomoto^I; Beny Schmidt^II; Alberto Alain Gabbai^I

^IDisciplina de Neurologia. Escola Paulista de Medicina

^IIDepartamento de Anatomia Patológica. Escola Paulista de Medicina

RESUMO

A paralisia periódica é entidade caracterizada por crises de fraqueza muscular relacionadas com alterações do nível sérico de potássio. A biópsia muscular pode mostrar alterações específicas ou inespecíficas. Nosso estudo tem como objetivo a análise de 17 biópsias musculares de 14 pacientes com paralisia periódica (14 hipocalêmica, 2 hipercalêmica). Todas as biópsias mostraram alguma alteração histopatológica. Quatorze biópsias apresentavam vacúolos, que se caracterizavam por serem únicos, de localização periférica, de aparecimento frequente e preferentemente em fibras do tipo I. Os vacúolos eram mais visualizados naqueles pacientes com longa evolução e sem relação com a frequência de crises. Os agregados tubulares foram encontrados em 10 biópsias principalmente naqueles pacientes com crises frequentes e doença de longa evolução. Em 3 pacientes foram realizadas 2 biópsias, notando-se piora das alterações em 2. Um paciente evoluiu com quadro clínico de miopatia permanente, confirmado pela biópsia muscular. Alterações inespecíficas foram encontradas em graus variáveis em 15 biópsias. Nosso estudo mostra que os vacúolos e os agregados tubulares são achados frequentes na paralisia periódica, constituindo importante auxílio diagnóstico. Alterações miopáticas evidentes à biópsia sugerem o aparecimento de miopatia permanente, quadro decorrente de doença de longa evolução ou crises severas.

Palavras-chave: paralisia periódica, biópsia, músculo esquelético, histotogia, vacúolos, agregados tubulares.

SUMMARY

Periodic paralysis is a rare disease, characterized by transient weakness associated with abnormal levels of serum potassium. Muscle biopsy may show a wide range of abnormalities, vacuoles being more specifically linked to the disease. We analysed 17 muscle biopsies from 14 patients with periodic paralysis (14 hypokalemic, 2 hyperkalemic). All of them showed at least one histological abnormality. Fourteen specimens showed vacuoles that were peripheral, single, frequent and preferentially found in type I fibers. Frequency or severity of attacks did not correlate with the presence of vacuoles but those were more easily found in patients with long term disease. Ten biopsies showed tubular aggregates, specially on the patients with frequent crises or long term disease. A second biopsy was done in three patients and in two we observed a worsening of the histopathologic picture. One patient manifested interictal weakness with evident myopathic changes on the muscle biopsy. Nonspecific changes were found in variable degrees in 15 biopsies. Our study shows that vacuoles and tubular aggregates are frequent changes in periodic paralysis and therefore helpful for the diagnosis. Important myopathic findings in the muscle biopsy suggest a permanent myopathy which probably develops after severe crises or long term disease.

Key words: periodic paralysis, biopsy, skeletal muscle, vacuoles, tubular aggregates.

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Aceite: 21-setembro-1993.

Dra. Célia Harumi Tengan - Disciplina de Neurologia, Escola Paulista de Medicina - Rua Botucatu 762 - 04023-900 São Paulo SP - Brasil.

1. Biczyskowa W, Fidzianska A, Jedrzejowska H. Light and electron microscopic study of the muscles in hypokalemic periodic paralysis. Acta Neuropath (Berl) 1969, 12:329-338.
2. Bradley WG. Adynamia episódica hereditaria: clinical, pathological and electrophysiological studies in an affected family. Brain 1969, 92:345-378.
3. Bradley WG. Ultrastructural changes in adynamia episódica hereditaria and normokalaemic familial periodic paralysis. Brain 1969, 92:379-390.
4. Bradley WG, Taylor R, Rice DR, Hausmanowa-Petruzewicz I, Adelman LS, Jenkison M, Jedrzejowska H, Drac H, Pendlebeury WW. Progressive myopathy in hyperkalemic periodic paralysis. Arch Neurol 1990, 47:1013-1017.
5. Buruma OJS, Bots GTAM, Went LN. Familial hypokalemic periodic paralysis: 50 year follow-up of a large family. Arch Neurol 1985, 42:28-31.
6. Carson, MJ, Pearson CM. Familial hyperkalemic periodic paralysis with myotonic features. J Pediat 1964, 64:853-865.
7. Cheah JS, Tock EPC, Kan SP. The light and electron microscopic changes in the skeletal muscles during paralysis in thyrotoxic periodic paralysis. Am J Med Sci 1975, 269:365-374.
8. Chesson AL, Schochet SS, Peters BH. Biphasic periodic paralysis. Arch Neurol 1979, 36:700-704.
9. Chui LA, Neustein H, Munsat TL. Tubular aggregates in subclinical alcoholic myopathy. Neurology 1975, 25:405-412.
10. Dubowitz V, Brooke MH. Muscle biopsy: a modern approach. London: Saunders, 1973.
11. Engel AG. Evolution and content of vacuoles in primary hypokalemic periodic paralysis. Mayo Clin Proc 1970, 45:774-814.
12. Engel AG. Periodic paralysis. In: Engel AG, Banker BO, Myology. New York: McGraw Hill, 1986, p.1843-1870.
13. Fontaine B, Khurana TS, Hoffman EP, Bruns G, Haines JL, Trofatter J A, Hanson MP, Rich J, McFarlane H, Yasek DM, Romano D, Gusella JF, Brown RH Jr. Hyperkalemic periodic paralysis and the adult muscle sodium channel gene. Science 1990, 250:1000-1002.
14. Gilchrist JM, Ambler M, Agatiello P. Steroid-responsive tubular aggregate myopathy. Muscle & Nerve 1991, 14:233-236.
15. Gordon AM, Green JR, Lagunoff D. Studies on a patient with hypokalemic familial periodic paralysis. Am J Med 1970, 48:185-195.
16. Gruner JE. Anomalies du reticulum sarcoplasmique et prolifération de tubules dans le muscle d'une paralysie périodique familiale. C R SocBiol (Paris) 1966, 160:193-196.
17. Howes EL, Price HM, Pearson CM, Blumberg JM. Hypokalemic periodic paralysis electromicroscopic changes in the sarcoplasm. Neurology 1966, 16:242-256.
18. Ionasescu V, Schochet SS, Powers JM, Koob K, Conway TW. Hypokalemic periodic paralysis: low activity of sarcoplasmic reticulum and muscle ri bo somes during induced attack. J Neurol Sci. 1974, 21:419-429.
19. Lázaro RP, Fenichel GM, Kilroy AW, Saito A, Fleicher S. Cramps, muscle pain and tubular aggregates. Arch Neurol 1980, 37:715-717.
20. Koch MC, Ricker K, Otto M, Grimm T, Hoffman EP, Rüdel R, Bender K, Zoll B, Harper PS, Lehmann-Horn F. Confirmation of linkage of hyperkalaemic periodic paralysis to choromosome 17. J. Med. Genet. 1991, 28:583-586.
21. Marchiori P, Scaff M, Levy JA, Callegaro D, Assis JL. Paralisia periódica familiar: estudo de oito casos. Arq. Neuropsiquiatr 1980, 38:391-398.
22. Martin JE, Mather K, Swash M, Gray AB. Expression of heat shock protein epitopes in tubular aggregates. Muscle Nerve 1991, 14:219-225.
23. Meyers KR, Gilden OH, Rinaldi CF, Hansen JL. Periodic muscle weakness, normokalemia and tubular aggregates. Neurology 1972, 22:269-279.
24. Odor DL, Patel AN, Pearce LA Familial hypokalemic periodic paralysis with permanent myopathy. J Neuropath Exp Neurol 1967, 26:98-114.
25. Ptacek U, Gouw L, Kwiecinski H, McManis P, Endell JR, Barohn R, George AL, Barchi RL, Robertson M, Leppert F. Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis. Ann Neurol 1993, 33:300-307.
26. Ptacek LJ, Tyler F, Trimmer JS, Agnew WS, Leppert M. Analysis in a large hyperkalemic periodic paralysis pedigree supports tight linkage to a sodium channel locus. Am J Hum Genet 1991, 49:378-382.
27. Ricker K, Camacho LM, Grafe P, Lehmann-Horn F, Rüdel R. Adynamia episódica hereditaria: what causes the weakness? Muscle Nerve 1989, 12:883-891.
28. Rojas CV, Wang J, Schwartz LS, Hoffman EP, Powell BR, Brown Jr RH. A met-to-val mutation in the skeletal muscle. Na channel a-subunit in hyperkalaemic periodic paralysis. Nature 1991, 354:387-389.
29. Rüdel R, Lehmann-Horn F, Ricker K, Küther G. Hypokalemic periodic paralysis in vitro investigation of muscle fiber membrane parameters. Muscle Nerve 1984, 7:110-120.
30. Schmidt B, Gabbai AA Oliveira ASB, Braga-Junior B, Castelo A Filho, Laredo-Filho J. A biópsia muscular:nova metodologia "a dança dos farabeufs". Rev. Bras. Ortopedia 1988, 23:21-26.
31. Schotland D. Ultrastrutural abnormalities in myotonic dystrophy including an unusual T-system alternation. J Neuropath Exp Neurol 1968,27:109-110.
32. Shy GM, Wanko T, Rowley PT, Engel AG. Studies in familial periodic paralysis. Exp Neurol 1961, 3:53-121.
33. Tome FMS. Periodic paralysis and electrolyte disorders. In: Mastaglia FL, Walton J. (eds) Skeletal muscle patthology. Edinburgh: Churchill Livingstone 1982, p.287-308.
34. Vroom FQ, Jarrell MA, Maren TH. Acetazolamide treatment of hypokalemic periodic paralysis probable mechanism of action. Arch Neurol 1975, 32:385-392.
35. Weraeck LC. O valor da biópsia muscular em neurologia: análise de 290 exames a fresco e pela histoquímica. Rev Bras Clin Terap 1981,10 (Ed. Especial):2-24.

Datas de Publicação

Publicação nesta coleção
19 Jan 2011
Data do Fascículo
Mar 1994

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

[1] 1. Biczyskowa W, Fidzianska A, Jedrzejowska H. Light and electron microscopic study of the muscles in hypokalemic periodic paralysis. Acta Neuropath (Berl) 1969, 12:329-338.

[2] 2. Bradley WG. Adynamia episódica hereditaria: clinical, pathological and electrophysiological studies in an affected family. Brain 1969, 92:345-378.

[3] 3. Bradley WG. Ultrastructural changes in adynamia episódica hereditaria and normokalaemic familial periodic paralysis. Brain 1969, 92:379-390.

[4] 4. Bradley WG, Taylor R, Rice DR, Hausmanowa-Petruzewicz I, Adelman LS, Jenkison M, Jedrzejowska H, Drac H, Pendlebeury WW. Progressive myopathy in hyperkalemic periodic paralysis. Arch Neurol 1990, 47:1013-1017.

[5] 5. Buruma OJS, Bots GTAM, Went LN. Familial hypokalemic periodic paralysis: 50 year follow-up of a large family. Arch Neurol 1985, 42:28-31.

[6] 6. Carson, MJ, Pearson CM. Familial hyperkalemic periodic paralysis with myotonic features. J Pediat 1964, 64:853-865.

[7] 7. Cheah JS, Tock EPC, Kan SP. The light and electron microscopic changes in the skeletal muscles during paralysis in thyrotoxic periodic paralysis. Am J Med Sci 1975, 269:365-374.

[8] 8. Chesson AL, Schochet SS, Peters BH. Biphasic periodic paralysis. Arch Neurol 1979, 36:700-704.

[9] 9. Chui LA, Neustein H, Munsat TL. Tubular aggregates in subclinical alcoholic myopathy. Neurology 1975, 25:405-412.

[10] 10. Dubowitz V, Brooke MH. Muscle biopsy: a modern approach. London: Saunders, 1973.

[11] 11. Engel AG. Evolution and content of vacuoles in primary hypokalemic periodic paralysis. Mayo Clin Proc 1970, 45:774-814.

[12] 12. Engel AG. Periodic paralysis. In: Engel AG, Banker BO, Myology. New York: McGraw Hill, 1986, p.1843-1870.

[13] 13. Fontaine B, Khurana TS, Hoffman EP, Bruns G, Haines JL, Trofatter J A, Hanson MP, Rich J, McFarlane H, Yasek DM, Romano D, Gusella JF, Brown RH Jr. Hyperkalemic periodic paralysis and the adult muscle sodium channel gene. Science 1990, 250:1000-1002.

[14] 14. Gilchrist JM, Ambler M, Agatiello P. Steroid-responsive tubular aggregate myopathy. Muscle & Nerve 1991, 14:233-236.

[15] 15. Gordon AM, Green JR, Lagunoff D. Studies on a patient with hypokalemic familial periodic paralysis. Am J Med 1970, 48:185-195.

[16] 16. Gruner JE. Anomalies du reticulum sarcoplasmique et prolifération de tubules dans le muscle d'une paralysie périodique familiale. C R SocBiol (Paris) 1966, 160:193-196.

[17] 17. Howes EL, Price HM, Pearson CM, Blumberg JM. Hypokalemic periodic paralysis electromicroscopic changes in the sarcoplasm. Neurology 1966, 16:242-256.

[18] 18. Ionasescu V, Schochet SS, Powers JM, Koob K, Conway TW. Hypokalemic periodic paralysis: low activity of sarcoplasmic reticulum and muscle ri bo somes during induced attack. J Neurol Sci. 1974, 21:419-429.

[19] 19. Lázaro RP, Fenichel GM, Kilroy AW, Saito A, Fleicher S. Cramps, muscle pain and tubular aggregates. Arch Neurol 1980, 37:715-717.

[20] 20. Koch MC, Ricker K, Otto M, Grimm T, Hoffman EP, Rüdel R, Bender K, Zoll B, Harper PS, Lehmann-Horn F. Confirmation of linkage of hyperkalaemic periodic paralysis to choromosome 17. J. Med. Genet. 1991, 28:583-586.

[21] 21. Marchiori P, Scaff M, Levy JA, Callegaro D, Assis JL. Paralisia periódica familiar: estudo de oito casos. Arq. Neuropsiquiatr 1980, 38:391-398.

[22] 22. Martin JE, Mather K, Swash M, Gray AB. Expression of heat shock protein epitopes in tubular aggregates. Muscle Nerve 1991, 14:219-225.

[23] 23. Meyers KR, Gilden OH, Rinaldi CF, Hansen JL. Periodic muscle weakness, normokalemia and tubular aggregates. Neurology 1972, 22:269-279.

[24] 24. Odor DL, Patel AN, Pearce LA Familial hypokalemic periodic paralysis with permanent myopathy. J Neuropath Exp Neurol 1967, 26:98-114.

[25] 25. Ptacek U, Gouw L, Kwiecinski H, McManis P, Endell JR, Barohn R, George AL, Barchi RL, Robertson M, Leppert F. Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis. Ann Neurol 1993, 33:300-307.

[26] 26. Ptacek LJ, Tyler F, Trimmer JS, Agnew WS, Leppert M. Analysis in a large hyperkalemic periodic paralysis pedigree supports tight linkage to a sodium channel locus. Am J Hum Genet 1991, 49:378-382.

[27] 27. Ricker K, Camacho LM, Grafe P, Lehmann-Horn F, Rüdel R. Adynamia episódica hereditaria: what causes the weakness? Muscle Nerve 1989, 12:883-891.

[28] 28. Rojas CV, Wang J, Schwartz LS, Hoffman EP, Powell BR, Brown Jr RH. A met-to-val mutation in the skeletal muscle. Na channel a-subunit in hyperkalaemic periodic paralysis. Nature 1991, 354:387-389.

[29] 29. Rüdel R, Lehmann-Horn F, Ricker K, Küther G. Hypokalemic periodic paralysis in vitro investigation of muscle fiber membrane parameters. Muscle Nerve 1984, 7:110-120.

[30] 30. Schmidt B, Gabbai AA Oliveira ASB, Braga-Junior B, Castelo A Filho, Laredo-Filho J. A biópsia muscular:nova metodologia "a dança dos farabeufs". Rev. Bras. Ortopedia 1988, 23:21-26.

[31] 31. Schotland D. Ultrastrutural abnormalities in myotonic dystrophy including an unusual T-system alternation. J Neuropath Exp Neurol 1968,27:109-110.

[32] 32. Shy GM, Wanko T, Rowley PT, Engel AG. Studies in familial periodic paralysis. Exp Neurol 1961, 3:53-121.

[33] 33. Tome FMS. Periodic paralysis and electrolyte disorders. In: Mastaglia FL, Walton J. (eds) Skeletal muscle patthology. Edinburgh: Churchill Livingstone 1982, p.287-308.

[34] 34. Vroom FQ, Jarrell MA, Maren TH. Acetazolamide treatment of hypokalemic periodic paralysis probable mechanism of action. Arch Neurol 1975, 32:385-392.

[35] 35. Weraeck LC. O valor da biópsia muscular em neurologia: análise de 290 exames a fresco e pela histoquímica. Rev Bras Clin Terap 1981,10 (Ed. Especial):2-24.