Corticosteroides no tratamento da miastenia grave. Estudo de 12 casos com revisão da literatura

Assis, José Lamartine de

doi:10.1590/S0004-282X1975000100004

Resumos

Foram estudados os resultados do tratamento da miastenia grave em 12 pacientes, sendo 10 com a forma generalizada severa, um com a forma generalizada moderada e um com miastenia acentuada associada a polimiosite. Sete pacientes foram previamente timectomizados e somente um apresentava timoma. Todos estavam em uso de doses elevadas de drogas anticolinesterásicas com resposta terapêutica pobre ou nula. Um paciente foi tratado com dexametaxona, outro com dexametazona seguida de prednisona e os restantes com prednisona, sempre em doses altas inicialmente (100 mg por dia ou em dias alternados) e com redução gradativa ulterior até doses de manutenção. Os corticosteróides foram administrados sempre pela via oral, por períodos que variaram de duas semanas até dois anos e meio. Em conclusão, 75% de 12 pacientes com miastenia grave generalizada foram influenciados favoravelmente com este método terapêutico. Deste grupo apenas um apresentava timoma e não respondeu a qualquer tratamento. Outro paciente apresentava polimiosite associada e teve excelente resposta terapêutica. Dois miastênicos sem timoma tiveram a sintomatologia exacerbada durante o tratamento. Nenhum efeito colateral importante foi observado, mesmo nos pacientes tratados a longo prazo.

The results of treatment of myasthenia gravis in 12 patients are reported. There were 10 cases with severe generalized form and two cases with moderate generalized form, one of which associated with polymyositis. Seven patients had prior thymectomy and one of them had a thymoma. All the patients were receiving anticholinesterase drugs with poor response or without any response. One patient received a short, intensive course of dexametazone, and other patient used prednisone after a more prolonged dexametazone course. The remaining patients received prednisone, always beginning with high (100 mg) alternate day oral single-doses. This therapy has been maintained for a period thought to be sufficient to suppress the symptoms, as well as to allow remission or an improvement for remaining even when prednisone had been slowly decreased, after a scheduled of one to two years of treatment. In conclusion, 75% of 12 patients with generalized myasthenia gravis showed improvement or complete remission of symptoms during the corticosteroid therapy. There was only a case with thymoma that showed no response to all treatments. Other patient had a polymyositis associated with myasthenia gravis and showed an excellent therapeutic result. Two patients without thymoma showed an initial worsening. To date no important side effect was noted including in the patients treated for a long period.

Corticosteroides no tratamento da miastenia grave. Estudo de 12 casos com revisão da literatura

Corticosteroids in the management of myasthenia gravis

José Lamartine de Assis

Professor Adjunto de Clínica Neurológica do Departamento de Neuropsiquiatria da Faculdade de Medicina da Universidade de São Paulo

RESUMO

Foram estudados os resultados do tratamento da miastenia grave em 12 pacientes, sendo 10 com a forma generalizada severa, um com a forma generalizada moderada e um com miastenia acentuada associada a polimiosite. Sete pacientes foram previamente timectomizados e somente um apresentava timoma. Todos estavam em uso de doses elevadas de drogas anticolinesterásicas com resposta terapêutica pobre ou nula. Um paciente foi tratado com dexametaxona, outro com dexametazona seguida de prednisona e os restantes com prednisona, sempre em doses altas inicialmente (100 mg por dia ou em dias alternados) e com redução gradativa ulterior até doses de manutenção. Os corticosteróides foram administrados sempre pela via oral, por períodos que variaram de duas semanas até dois anos e meio.

Em conclusão, 75% de 12 pacientes com miastenia grave generalizada foram influenciados favoravelmente com este método terapêutico. Deste grupo apenas um apresentava timoma e não respondeu a qualquer tratamento. Outro paciente apresentava polimiosite associada e teve excelente resposta terapêutica. Dois miastênicos sem timoma tiveram a sintomatologia exacerbada durante o tratamento. Nenhum efeito colateral importante foi observado, mesmo nos pacientes tratados a longo prazo.

SUMMARY

The results of treatment of myasthenia gravis in 12 patients are reported. There were 10 cases with severe generalized form and two cases with moderate generalized form, one of which associated with polymyositis. Seven patients had prior thymectomy and one of them had a thymoma. All the patients were receiving anticholinesterase drugs with poor response or without any response. One patient received a short, intensive course of dexametazone, and other patient used prednisone after a more prolonged dexametazone course. The remaining patients received prednisone, always beginning with high (100 mg) alternate day oral single-doses. This therapy has been maintained for a period thought to be sufficient to suppress the symptoms, as well as to allow remission or an improvement for remaining even when prednisone had been slowly decreased, after a scheduled of one to two years of treatment.

In conclusion, 75% of 12 patients with generalized myasthenia gravis showed improvement or complete remission of symptoms during the corticosteroid therapy. There was only a case with thymoma that showed no response to all treatments. Other patient had a polymyositis associated with myasthenia gravis and showed an excellent therapeutic result. Two patients without thymoma showed an initial worsening. To date no important side effect was noted including in the patients treated for a long period.

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Clínica Neurológica Faculdade de Medicina, Universidade de São Paulo Caixa Postal 3461 01000 São Paulo, SP Brasil.

1. ASSIS, J. L. Tratamento dos casos graves de miastenia. Ação do ACTH e cortisona. Arq. Neuro-Psiquiat. (São Paulo) 14:28, 1956.
2. ASSIS, J. L. Tratamento das formas severas de miastenia grave pelo ACTH por via intravenosa. Arq. Neuro-Psiquiat. (São Paulo) 18:359, 1960.
3. ASSIS, J. L. Tratamento atual da miastenia grave. Rev. paul. Med. (São Paulo) 67:231, 1965.
4. BRUNNER, N. G.; NAMBA, T. & GROB, D. Corticosteroids in management of severe, generalized myasthenia gravis. Effectiveness and comparison with corticotropin therapy. Neurology (Minneapolis) 22:603, 1972.
5. CAPE, C. A. & UTTERBACK, R. A. Treatment of myasthenia gravis with adrenocorticotropic hormone (ACTH): massive short-term and maintenance treatment. J. Neurol. Neurosurg. Psychiat. 32:290, 1969.
6. DOUGHERTY, T. F. & WHITE, A. Effect of pituitary adrenotropic hormone on lymphoid tissue. Proc. Soc. exp. Biol. Med. 53:132, 1943.
7. - ENGEL, W. K. & WARMOLTS, J. R. Myasthenia gravis: a new hypothesis of the pathogenesis and a new form of treatment. Ann. N.Y. Acad. Sci. 183:72, 1971.
8. FREYDBERG, L. D. The place of corticotropin in the treatment of myasthenia gravis. Ann. intern. Med. 52:806, 1960.
9. GRIGGS, R. C; McFARLIN, D. E. & ENGEL, W. K. Severe occult juvenile myasthenia gravis responsive to long-term corticosteroid therapy. Trans. Am. neurol. Ass. 93:216, 1968.
10. GROB, D. & HARVEY, A. M. Effect of adrenocorticotropic hormone (ACTH) and cortisone administration in patients with myasthenia gravis and report of onset of myasthenia gravis during prolonged cortisone administration. Bull. John Hopkins Hosp. 91:124, 1952.
11. GROB, D. & NAMBA, T. Corticotropin in generalized myasthenia gravis. Effect of short, intensive courses. J. Am. med. Ass. 198:703, 1966.
12. GOULON, M.; NOUAILHAT, F.; BAROIS, A.; GROSBUIS, S. & JORON, M. H. Traitement de la myasthénie par les adrénocorticotrophines (ACTH et Synacthène). A propos de 100 cures chez 25 malades. Revue neurol. (Paris) 127:457, 1972.
13. JOHNS, T. R.; CROWLEY, W. J.; MILLER, J. Q. & CAMPA, J. F. The syndrome of myasthenia and polymyositis with comments on therpay. Ann. N.Y. Acad. Sci. 183:64, 1971.
14. KANE, C. A. The effect of certain endocrine glands on myasthenia gravis. Am. J. Med. 19:729, 1955.
15. KJAER, M. Myasthenia gravis and myasthenic syndromes treated with prednisone. Acta psychiat. neurol. scand. 47:464, 1971.
16. MERTENS, H. G.; BALZEREIT, F. & LEIPERT, M. The treatment of severe myasthenia gravis with immunosuppressive agents. Europ. Neurol. 2:321, 1969.
17. MILLIKAN, C. H. & EATON, L. M. Clinical evaluation of ACTH and cortisone in myasthenia gravis. Neurology (Minneapolis) 1:145, 1951.
18. NAMBA, T.; BRUNNER, N. G.; SHAPIRO, M. S. & GROB, D. Corticotropin therapy in myasthenia gravis: effects, indications and limitations. Neurology (Minneapolis) 21:1008, 1971.
19. NAMBA, T.; ARIMORI, S. & GROB, D. Effect on mice of intravenous administration of lymphocytes from normal subjects and from patients with myasthenia gravis. Neurology (Minneapolis) 19:461, 1969.
20. NAMBA, T.; ARIMORI, S. & GROB, D. Lymphocytes of patients with myasthenia gravis: local effects in rats following intramuscular administration. Arch. Neurol. (Chicago) 21:285, 1969.
21. NAMBA, T. & SHAPIRO, M. S. Corticotropin therapy in patients with myasthenia gravis: steroid metabolism, and histology of skeletal muscle and thymus. J. neurol. Sci. 16:165, 1972.
22. OSSERMAN, K. E. Studies in myasthenia gravis. N.Y. St. J. Med. 56:2512, 1956.
23. OSSERMAN, K. E. & GENKINS, G. Studies in myasthenia gravis: short-term massive corticotropin therapy. J. Am. med. Ass. 198:699, 1966.
24. OSSERMAN, K. E. Muscles (myasthenia gravis). In MIESCHER, P. A. & MÜLLER EBERHARD, H. J. Textbook of Immunopathology. Grune & Statton, New York, 1969. p. 607.
25. SCHLEZINGER, N. S. Present status of therapy in myasthenia gravis. J. Am. med. Ass. 148:508, 1952.
26. SHAPIRO, M. S.; NAMBA, T. & GROB, D. Corticotropin therapy and thymectomy in management of myasthenia gravis. Arch. Neurol. (Chicago) 24:65, 1971.
27. SHAPIRO, M. S.; NAMBA, T. & BRUNNER, N. G. Role of adrenocorticosteroids in mediation of therapeutic effect of corticotropin in severe, generalized myasthenia gravis. J. clin. Invest. 50:84, 1971.
28. SHY, G. M.; BRENDLER, S.; RABINOVITCH, R. & McEACHERN, D. Effects of cortisone in certain neuromuscular disorders. J. Am. med. Ass. 144:1353, 1950.
29. SIMPSON, M. E.; LI, C. H.; REINHARDT, W. O. & EVANS, M. H. Similarity of response of thymus and lymph nodes to administration of adrenocorticotropic hormone in the rat. Proc. Soc. exp. Biol. Med. 54:135, 1943.
30. SOFFER, L. J.; GABRILOVE, J. L.; LAQUEUR, H P.; VOLTERRA, M.; JACOBS, M. D. & SUSSMAN, M. L. The effects of anterior pituitary adrenocorticotrophic hormone (ACTH) in myasthenia gravis with tumor of the thymus. J. Mt. Sinai Hosp. 15:73, 1948.
31. TORDA, C. & WOLFF, H. G. Effect of adrenocorticotrophic hormone of pituitary gland on ability of tissue to synthesize acetylcholine. Proc. Soc. exp. Biol. Med. 57:137, 1944.
32. TORDA, C. & WOLFF, H. G. Effects of adrenocorticotrophic hormone on neuromuscular function in patients with myasthenia gravis. J. clin. Invest. 28:1228, 1949.
33. TORDA, C. & WOLFF, H. G. Effects of administration of the adrenocorticotropic hormone (ACTH) on patients with myasthenia gravis. Arch. Neurol. Psychiat. (Chicago) 66:163, 1951.
34. TUNCBAY, T. O.; KETEL, W. B. & BOSHES, B. Cortisone effects on myoneural junction. Neurology (Minneapolis) 15:314, 1965.
35. VON REIS, G.; LILJESTRAND, A. & MATELL, G. Treatment of severe myasthenia gravis with large doses of ACTH. Ann. N.Y. Acad. Sci. 135:409, 1966.
36. WARMOLTS, J. R. & ENGEL, W. K. Benefit from alternate-day prednisone in myasthenia gravis. New England J. Med. 286:17, 1972.
37. WESTERBERG, M. R. & MAGEE, K. R. Treatment review: myasthenia gravis. Neurology (Minneapolis) 5:728, 1955.
38. WHITE, A. & DONGHTY, T. F. Influence of pituitary adrenotrophic hormone on lymphoid tissue structure in relation to serum proteins. Proc. Soc. exp. Biol. Med. 56:26, 1944.

Datas de Publicação

Publicação nesta coleção
09 Abr 2013
Data do Fascículo
Mar 1975

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

[1] 1. ASSIS, J. L. Tratamento dos casos graves de miastenia. Ação do ACTH e cortisona. Arq. Neuro-Psiquiat. (São Paulo) 14:28, 1956.

[2] 2. ASSIS, J. L. Tratamento das formas severas de miastenia grave pelo ACTH por via intravenosa. Arq. Neuro-Psiquiat. (São Paulo) 18:359, 1960.

[3] 3. ASSIS, J. L. Tratamento atual da miastenia grave. Rev. paul. Med. (São Paulo) 67:231, 1965.

[4] 4. BRUNNER, N. G.; NAMBA, T. & GROB, D. Corticosteroids in management of severe, generalized myasthenia gravis. Effectiveness and comparison with corticotropin therapy. Neurology (Minneapolis) 22:603, 1972.

[5] 5. CAPE, C. A. & UTTERBACK, R. A. Treatment of myasthenia gravis with adrenocorticotropic hormone (ACTH): massive short-term and maintenance treatment. J. Neurol. Neurosurg. Psychiat. 32:290, 1969.

[6] 6. DOUGHERTY, T. F. & WHITE, A. Effect of pituitary adrenotropic hormone on lymphoid tissue. Proc. Soc. exp. Biol. Med. 53:132, 1943.

[7] 7. - ENGEL, W. K. & WARMOLTS, J. R. Myasthenia gravis: a new hypothesis of the pathogenesis and a new form of treatment. Ann. N.Y. Acad. Sci. 183:72, 1971.

[8] 8. FREYDBERG, L. D. The place of corticotropin in the treatment of myasthenia gravis. Ann. intern. Med. 52:806, 1960.

[9] 9. GRIGGS, R. C; McFARLIN, D. E. & ENGEL, W. K. Severe occult juvenile myasthenia gravis responsive to long-term corticosteroid therapy. Trans. Am. neurol. Ass. 93:216, 1968.

[10] 10. GROB, D. & HARVEY, A. M. Effect of adrenocorticotropic hormone (ACTH) and cortisone administration in patients with myasthenia gravis and report of onset of myasthenia gravis during prolonged cortisone administration. Bull. John Hopkins Hosp. 91:124, 1952.

[11] 11. GROB, D. & NAMBA, T. Corticotropin in generalized myasthenia gravis. Effect of short, intensive courses. J. Am. med. Ass. 198:703, 1966.

[12] 12. GOULON, M.; NOUAILHAT, F.; BAROIS, A.; GROSBUIS, S. & JORON, M. H. Traitement de la myasthénie par les adrénocorticotrophines (ACTH et Synacthène). A propos de 100 cures chez 25 malades. Revue neurol. (Paris) 127:457, 1972.

[13] 13. JOHNS, T. R.; CROWLEY, W. J.; MILLER, J. Q. & CAMPA, J. F. The syndrome of myasthenia and polymyositis with comments on therpay. Ann. N.Y. Acad. Sci. 183:64, 1971.

[14] 14. KANE, C. A. The effect of certain endocrine glands on myasthenia gravis. Am. J. Med. 19:729, 1955.

[15] 15. KJAER, M. Myasthenia gravis and myasthenic syndromes treated with prednisone. Acta psychiat. neurol. scand. 47:464, 1971.

[16] 16. MERTENS, H. G.; BALZEREIT, F. & LEIPERT, M. The treatment of severe myasthenia gravis with immunosuppressive agents. Europ. Neurol. 2:321, 1969.

[17] 17. MILLIKAN, C. H. & EATON, L. M. Clinical evaluation of ACTH and cortisone in myasthenia gravis. Neurology (Minneapolis) 1:145, 1951.

[18] 18. NAMBA, T.; BRUNNER, N. G.; SHAPIRO, M. S. & GROB, D. Corticotropin therapy in myasthenia gravis: effects, indications and limitations. Neurology (Minneapolis) 21:1008, 1971.

[19] 19. NAMBA, T.; ARIMORI, S. & GROB, D. Effect on mice of intravenous administration of lymphocytes from normal subjects and from patients with myasthenia gravis. Neurology (Minneapolis) 19:461, 1969.

[20] 20. NAMBA, T.; ARIMORI, S. & GROB, D. Lymphocytes of patients with myasthenia gravis: local effects in rats following intramuscular administration. Arch. Neurol. (Chicago) 21:285, 1969.

[21] 21. NAMBA, T. & SHAPIRO, M. S. Corticotropin therapy in patients with myasthenia gravis: steroid metabolism, and histology of skeletal muscle and thymus. J. neurol. Sci. 16:165, 1972.

[22] 22. OSSERMAN, K. E. Studies in myasthenia gravis. N.Y. St. J. Med. 56:2512, 1956.

[23] 23. OSSERMAN, K. E. & GENKINS, G. Studies in myasthenia gravis: short-term massive corticotropin therapy. J. Am. med. Ass. 198:699, 1966.

[24] 24. OSSERMAN, K. E. Muscles (myasthenia gravis). In MIESCHER, P. A. & MÜLLER EBERHARD, H. J. Textbook of Immunopathology. Grune & Statton, New York, 1969. p. 607.

[25] 25. SCHLEZINGER, N. S. Present status of therapy in myasthenia gravis. J. Am. med. Ass. 148:508, 1952.

[26] 26. SHAPIRO, M. S.; NAMBA, T. & GROB, D. Corticotropin therapy and thymectomy in management of myasthenia gravis. Arch. Neurol. (Chicago) 24:65, 1971.

[27] 27. SHAPIRO, M. S.; NAMBA, T. & BRUNNER, N. G. Role of adrenocorticosteroids in mediation of therapeutic effect of corticotropin in severe, generalized myasthenia gravis. J. clin. Invest. 50:84, 1971.

[28] 28. SHY, G. M.; BRENDLER, S.; RABINOVITCH, R. & McEACHERN, D. Effects of cortisone in certain neuromuscular disorders. J. Am. med. Ass. 144:1353, 1950.

[29] 29. SIMPSON, M. E.; LI, C. H.; REINHARDT, W. O. & EVANS, M. H. Similarity of response of thymus and lymph nodes to administration of adrenocorticotropic hormone in the rat. Proc. Soc. exp. Biol. Med. 54:135, 1943.

[30] 30. SOFFER, L. J.; GABRILOVE, J. L.; LAQUEUR, H P.; VOLTERRA, M.; JACOBS, M. D. & SUSSMAN, M. L. The effects of anterior pituitary adrenocorticotrophic hormone (ACTH) in myasthenia gravis with tumor of the thymus. J. Mt. Sinai Hosp. 15:73, 1948.

[31] 31. TORDA, C. & WOLFF, H. G. Effect of adrenocorticotrophic hormone of pituitary gland on ability of tissue to synthesize acetylcholine. Proc. Soc. exp. Biol. Med. 57:137, 1944.

[32] 32. TORDA, C. & WOLFF, H. G. Effects of adrenocorticotrophic hormone on neuromuscular function in patients with myasthenia gravis. J. clin. Invest. 28:1228, 1949.

[33] 33. TORDA, C. & WOLFF, H. G. Effects of administration of the adrenocorticotropic hormone (ACTH) on patients with myasthenia gravis. Arch. Neurol. Psychiat. (Chicago) 66:163, 1951.

[34] 34. TUNCBAY, T. O.; KETEL, W. B. & BOSHES, B. Cortisone effects on myoneural junction. Neurology (Minneapolis) 15:314, 1965.

[35] 35. VON REIS, G.; LILJESTRAND, A. & MATELL, G. Treatment of severe myasthenia gravis with large doses of ACTH. Ann. N.Y. Acad. Sci. 135:409, 1966.

[36] 36. WARMOLTS, J. R. & ENGEL, W. K. Benefit from alternate-day prednisone in myasthenia gravis. New England J. Med. 286:17, 1972.

[37] 37. WESTERBERG, M. R. & MAGEE, K. R. Treatment review: myasthenia gravis. Neurology (Minneapolis) 5:728, 1955.

[38] 38. WHITE, A. & DONGHTY, T. F. Influence of pituitary adrenotrophic hormone on lymphoid tissue structure in relation to serum proteins. Proc. Soc. exp. Biol. Med. 56:26, 1944.