Penicilinoterapia intravenosa em altas doses na neurossífilis: estudo de 62 casos. I. Avaliação clínica

Nitrini, Ricardo; Spina-França, A.

doi:10.1590/S0004-282X1987000200002

Resumos

Sessenta e dois casos de neurossífilis sintomática foram tratados com penicilina G, na dose diária de 20 ou 24 milhões de UI,por via intravenosa, durante 15 a 30 dias. O tempo médio de acompanhamento após o tratamento foi de 30 meses. Aparecimento de novos sinais neurológicos depois do tratamento foi constatado em 13 pacientes. As formas clínicas apresentadas por esses pacientes eram: paralisia geral progressiva (9), taboparalisia (2), tabes dorsal (1) e neurossífilis meningovascular (1). Trinta e seis pacientes (58,1%) apresentaram melhora do quadro clinico, 22 (35,5%) não sofreram alteração e 4 pacientes (6,4%) pioraram clinicamente depois do tratamento. Em dois pacientes houve progressão para outras formas de neurossífilis. Os resultados clínicos da penicilinoterapia intravenosa constatados neste estudo não diferiram daqueles obtidos com penicilinoterapia intramuscular clássica registrados na literatura.

Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days. The mean follow-up time after the treatment was 30 months. Thirteen patients developed new neurological signs after the treatment. Their diagnosis were: general paresis (9), taboparesis (2), tabes dorsalis (1) and meningovascular neurosyphilis (1). After the treatment, thirty-six patients (58.1%) improved, 22 patients (35.5%) were unchanged and 4 patients (6.4%) deteriorated on clinical grounds. In two patients there was a progression to other forms of neurosyphilis. The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with classical intramuscular penicillin that were reported in the literature, from the clinical standpoint.

Penicilinoterapia intravenosa em altas doses na neurossífilis: estudo de 62 casos. I. Avaliação clínica

High-dose intravenous penicillin G in the treatment of neurosyphilis: a study of 62 patients. I. Clinical evaluation

Ricardo Nitrini^I; A. Spina-França^II

^IProfessor Assistente - Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (CN HC FMUSP)

^IIProfessor Titular - Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (CN HC FMUSP)

RESUMO

Sessenta e dois casos de neurossífilis sintomática foram tratados com penicilina G, na dose diária de 20 ou 24 milhões de UI,por via intravenosa, durante 15 a 30 dias. O tempo médio de acompanhamento após o tratamento foi de 30 meses. Aparecimento de novos sinais neurológicos depois do tratamento foi constatado em 13 pacientes. As formas clínicas apresentadas por esses pacientes eram: paralisia geral progressiva (9), taboparalisia (2), tabes dorsal (1) e neurossífilis meningovascular (1). Trinta e seis pacientes (58,1%) apresentaram melhora do quadro clinico, 22 (35,5%) não sofreram alteração e 4 pacientes (6,4%) pioraram clinicamente depois do tratamento. Em dois pacientes houve progressão para outras formas de neurossífilis. Os resultados clínicos da penicilinoterapia intravenosa constatados neste estudo não diferiram daqueles obtidos com penicilinoterapia intramuscular clássica registrados na literatura.

SUMMARY

Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days. The mean follow-up time after the treatment was 30 months. Thirteen patients developed new neurological signs after the treatment. Their diagnosis were: general paresis (9), taboparesis (2), tabes dorsalis (1) and meningovascular neurosyphilis (1). After the treatment, thirty-six patients (58.1%) improved, 22 patients (35.5%) were unchanged and 4 patients (6.4%) deteriorated on clinical grounds. In two patients there was a progression to other forms of neurosyphilis. The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with classical intramuscular penicillin that were reported in the literature, from the clinical standpoint.

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Clínica Neurológica, Hospital das Clínicas, FMUSP - Caixa Postal 34/61 - 01000 -São Paulo, SP - Brasil.

1. BOUDIN, G. - Paralysie générale. Rev. prat. (Paris) 16:3099, 1966.
2. CALLAWAY, J.L. ; FLOWER JR., A.H. ; HIRSCHMANN, V.R. & OLANSKY, S. -A four-year study of penicillin treatment of syphilis of the central nervous system. Sth. med. J. 43:412, 1950.
3. CHADI, C. & NITRINI, R. - Aspectos clínicos atuais da neurossífilis. In: Congresso Brasileiro de Neurología, 12. Temas Livres, Belo Horizonte, 1986.
4. COHEN, M.S. ; GIBSON, G. & OLARTE, M.R. - Lissauer form of paretic neurosyphilis: forgotten but not gone. Ann. Neurol. 12:219, 1982.
5. COLLART, P. ; BOREL, L.J. & DUREL, P. - Significance of spiral organisms found after treatment in late human and experimental syphilis. Brit. J. vener. Dis. 40:81, 1964.
6. COLLART, P. & POITEVIN, M. - Persistance des tréponèmes pâles après traitment au cours de la syphilis expérimentale et humaine. Ann. Med. Int. 126:223, 1975.
7. CUDDY, P.G. - Benzathine penicillin G in the treatment of neurosyphilis. Drug In tell. clin. Pharm. 16:205, 1982.
8. CURTIS, A.C. ; KRUSE, W.T. & NORTON, D.H. - Neurosyphilis. III. Evaluation after three years of treatment with penicillin alone and with a combination of penicillin and malaria. Amer. J. Syph. 33:527, 1949.
9. DANS, P.E. ; CAFFERTY, L, ; OTTER, S.E. & JOHNSON, R.J. - Innapropriate use of the cerebrospinal fluid venereal disease research laboratory (VDRL) to exclude neurosyphilis. Ann. int. Med. 104:86, 1986.
10. DATTNER, B. ; THOMAS, E.W. & WEXLER, G. - The Management of Neurosyphilis. Grune & Stratton, New York, 1944.
11. DATTNER, B. ; THOMAS, E.W. & MELLO, L. - Criteria for the management of neurosyphilis. Amer. J. Med. 10:463, 1951.
12. DUCAS, J. & ROBSON, H.J. - Cerebrospinal fluid penicillin levels during therapy for latent syphilis. J. amer. med. Assoc. 246:2583, 1981.
13. DUNLOP, E.M.C. ; AL-EGAILY, S.S. & HOUANG, E.T. - Penicillin levels in blood and CSF achieved by treatment of syphilis. J. amer. med. Assoc. 241:2538, 1979.
14. DUNLOP, E.M.C; AL-EGAILY, S.S. & HOUANG, E.T. - Production of treponemicidal concentration of penicillin in cerebrospinal fluid. Brit. med. J. 283:646, 1981.
15. EKBOM, K. - Carbamazepine in the treament of tabetic lightning pains. Arch. Neurol. (Chicago) 15:374, 1972.
16. FLETCHER, W.A. & SHARPE, J.A. - Tonic pupils in neurosyphilis. Neurology 36:188, 1986.
17. FORD, W.T. ; WIGALL, R.H. & STOKES, J.H. - Penicillin therapy of assymptomatic neurosyphilis: the spinal fluid cell count as a guide to therapeutic response and re-treament. Arch. int. Med. 88:235, 1951.
18. FOURNIER, A. - Leçons sur la Période Praeataxique du Tabes d'Origine Syphilitique. Masson, Paris, 1885.
19. GIMENEZ-ROLDAN, S. & MARTIN, M. - Tabetic lightning pains : high-dose intravenous penicillin versus carbamazepine therapy. Europ. Neurol. 20:424, 1981.
20. GREENE, B.M. ; MILLER, N.R. & BINUM, T.E. - Failure of penicillin G benzathine in the treatment of neurosyphilis. Arch. int. Med. 98:1117, 1980.
21. HAHN, R.D. - Some remarks on management of neurosyphilis. J. chronic Dis. 13:1, 1961.
22. HOOSHMAND, H. - Tabetic lightning pains. Arch. Neurol. (Chicago) 28:70, 1973.
23. HOOSHMAND, H. ; ESCOBAR, M.R. & KOPF, S.W. - Neuro-syphilis : a study of 241 patients. J. amer. med. Assoc. 219:726, 1972.
24. KOTEEN, H. ; DOTY, E. J. ; WEBSTER, B. & McDERMOTT, W. - Penicillin therapy in neurosyphilis. Amer. J. Syph. 31:1, 1947.
25. LANIGAN-O'KEEFFEE, F.M. - Return to normal of Argyll Robertson pupils after treatment. Brit. med. J. 2:1191, 1977.
26. LOWHAGEN, G.B. ; BRORSON, J.E. & KAIJSER, B. - Penicillin concentrations in cerebrospinal fluid and serum after intramuscular, intravenous and oral administration to syphilis patients. Acta derm-venereol. (Stockholm) 63:53, 1983.
27. LUXON, L.M. - Neurosyphilis. Internat. J. Derm. 19:310, 1980.
28. MAPELLI, G. - Must we revise our clinical concepts of tabetic neurosyphilis? Acta neurol. belg. 81:12, 1981.
29. MARTIN MORO, M.; BARTOLOME, P.; ANDRES, C. ; NUNEZ, A.G. ; MATEO, O. ; VILLANUEVA, J.A. & GIMENEZ-ROLDAN, S. - Penicilina intravenosa en el tratamiento de la neurosifilis. Arch. Neurobiol. (Madrid) 45:29, 1982.
30. MICHEL, D.; BLANC, A.; LAURENT, B. ; FOYATIER, N. & PORTFAIX, M. - Etude biologique, psychométrique et tomodensimétrique de la neurosyphilis traitée. Rev. neurol. (Paris) 139:737, 1983.
31. MOHR, J.A. ; GRIFFITHS, W. ; JACKSON, R. ; S A AD AH, H.; BIRD, P. & RIDDLE, J. - Neurosyphilis and penicillin levels in cerebrospinal fluid. J. amer. med. Assoc. 236:2208, 1976.
32. NITRINI, R. - (a) Neurossífilis : análise de alguns aspectos clínicos e laboratoriais. Tese, São Paulo, 1981. (b) Neurossífilis: penicilinoterapia intravenosa em altas doses. Tese. São Paulo, 1986.
33. N1TRINI. R.; BACHESCHI, L.A.; NÓBREGA, J.P.S.; SCAFF, M. & YASUDA, N. - Neurossífilis resistente a altas doses de penicilina: registro de um caso. Arq. Neuro-Psiquiat. (São Paulo) 42:55, 1984.
34. ORBAN, T. - Experience with a follow-up examination of 200 tabetic patients. Acta psychiat. scand. 32:89, 1957.
³⁵
ORGANIZAÇÃO MUNDIAL DE SAÚDE - Treponemal infections: report of a WHO scientific group. World Health Organization, Geneva, 1982.
36. OSELKA, G.W.; LEVI, G.C.: LOPES, H.V.; MENDONÇA, J.S.; BALDY, J.L.S.; TRABULSI, L.R. & AMATO NETO, V. - Antibióticos na Prática Médica. Gremed, São Paulo, 1978.
37. POLNIKORN, N.; WITOONPANICH, R.; VORACII1T, M.; VEJJAJIVA, S. & VEJJAJIVA, A. - Penicillin concentrations in the cerebrospinal fluid after benzathine penicillin and probenecid in the treatment of syphilis. Brit. J. vener. Dis. 58:342, 1982.
38. POLNIKORN, N.: WITOONPANICH, R.; VORACHIT, M.; VEJJAJIVA, S. & VEJJAJIVA, A. - Penicillin concentrations in cerebrospinal fluid after different treatment regimens for syphilis. Brit. J. vener. Dis. 56:363, 1980.
39. REIN, M.F. - Treatment of neurosyphilis. J. amer. med. Assoc. 246:2613, 1981.
40. RICE, N.S.C.; DUNLOP, E.M.C.; JONES, B.R.; HARE, M. J.; KING, A.J.; RODIN, P.; MUSHIN, A. & WILKINSON. A.E. - Demonstration of treponema-like forms in cases of treated and untreated late syphilis and of treated early syphilis. Brit. J. vener. Dis. 46:1, 1970.
41. ROMANOWSHI, B.: STARREVELD. E. & JAREMA, A.J. - Treatment of neurosyphilis with chloramphenicol: a case report. Brit. J. vener. Dis. 59:225, 1983.
42. ROSE. A.S. & SOLOMON. H.C. - Penicillin in the treatment of neurosyphilis. J. amer. med. Assoc. 133:5. 1947.
43. SCHMIDT. R.P. & GONYEA, E.F. - Neurosyphilis. In: A.B. Baker & R.J. Joynt - Clinical Neurology. Harper and Row, Philadelphia, 1980.
44. SEGAL, P.; JANISZEWSKA-GELDNER, B. & LEONOW1CZ-MICHNIOWSKA, J. - Results of penicillin therapy in syphilitic primary optic atrophy. Brit. J. vener. Dis. 36:257, 1960.
45. SIMON. R.P. - Neurosyphilis. Arch. Neurol. (Chicago) 42:606, 1985.
46. STOCKLI, H.R.; FOLLATH, F.: PROBST, A. & RUFLI, T. - Theraoieversager bei Neurolues (Falbericht) und Penicillinversagen im Liquor cerebrospinalis. Schweiz. Rdsch. med. Prax. 74:885, 1985.
47. TRAMONT. E.C. - Persistence of Treponema pallidum following; penicillin G therapy. J. amer. med. Assoc. 236:2206, 1976.
48. WEINSTEIN, J.M.; LEXOW, S.S.: HO, P. & SPICKARDS, A. - Acute syphilitic optic neuritis. Arch. Ophthal. 99:1392, 1981.
49. WILNER, E. & BRODY, J.A. - Prognosis of general paresis after treatment. Lancet 2:1370, 1968.
50. YOBS. A.R.: CLARK JR.. J.W.: MOTHERSHED, S.E.; BULLARD, J.C. & ARTLEY, C.W. - Further observations on the persistence of Treponema pallidum after treatment in rabbits and humans. Brit. J. vener. Dis. 44:116, 1968.
51. YODER, F.W. - Penicillin treatment of neurosyphilis: are recommended dosages sufficient? J. amer. med. Assoc. 232:270, 1975.
52. ZUKERMAN, E.; CARDOSO, W.; Di MIGUELI, H.; REIS FILHO, I.; SCHWARTZMAN, J.S.: BEI. A.; MOREIRA, M.H.; GIORGI, D.R.; ROTBERG, A. & REIS, J.B. - Incidência da neurossífilis * de sua» formas clínicas em São Paulo. Rev. paul. Med. 70:270, 1967.

Datas de Publicação

Publicação nesta coleção
22 Jun 2011
Data do Fascículo
Jun 1987

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

[1] 1. BOUDIN, G. - Paralysie générale. Rev. prat. (Paris) 16:3099, 1966.

[2] 2. CALLAWAY, J.L. ; FLOWER JR., A.H. ; HIRSCHMANN, V.R. & OLANSKY, S. -A four-year study of penicillin treatment of syphilis of the central nervous system. Sth. med. J. 43:412, 1950.

[3] 3. CHADI, C. & NITRINI, R. - Aspectos clínicos atuais da neurossífilis. In: Congresso Brasileiro de Neurología, 12. Temas Livres, Belo Horizonte, 1986.

[4] 4. COHEN, M.S. ; GIBSON, G. & OLARTE, M.R. - Lissauer form of paretic neurosyphilis: forgotten but not gone. Ann. Neurol. 12:219, 1982.

[5] 5. COLLART, P. ; BOREL, L.J. & DUREL, P. - Significance of spiral organisms found after treatment in late human and experimental syphilis. Brit. J. vener. Dis. 40:81, 1964.

[6] 6. COLLART, P. & POITEVIN, M. - Persistance des tréponèmes pâles après traitment au cours de la syphilis expérimentale et humaine. Ann. Med. Int. 126:223, 1975.

[7] 7. CUDDY, P.G. - Benzathine penicillin G in the treatment of neurosyphilis. Drug In tell. clin. Pharm. 16:205, 1982.

[8] 8. CURTIS, A.C. ; KRUSE, W.T. & NORTON, D.H. - Neurosyphilis. III. Evaluation after three years of treatment with penicillin alone and with a combination of penicillin and malaria. Amer. J. Syph. 33:527, 1949.

[9] 9. DANS, P.E. ; CAFFERTY, L, ; OTTER, S.E. & JOHNSON, R.J. - Innapropriate use of the cerebrospinal fluid venereal disease research laboratory (VDRL) to exclude neurosyphilis. Ann. int. Med. 104:86, 1986.

[10] 10. DATTNER, B. ; THOMAS, E.W. & WEXLER, G. - The Management of Neurosyphilis. Grune & Stratton, New York, 1944.

[11] 11. DATTNER, B. ; THOMAS, E.W. & MELLO, L. - Criteria for the management of neurosyphilis. Amer. J. Med. 10:463, 1951.

[12] 12. DUCAS, J. & ROBSON, H.J. - Cerebrospinal fluid penicillin levels during therapy for latent syphilis. J. amer. med. Assoc. 246:2583, 1981.

[13] 13. DUNLOP, E.M.C. ; AL-EGAILY, S.S. & HOUANG, E.T. - Penicillin levels in blood and CSF achieved by treatment of syphilis. J. amer. med. Assoc. 241:2538, 1979.

[14] 14. DUNLOP, E.M.C; AL-EGAILY, S.S. & HOUANG, E.T. - Production of treponemicidal concentration of penicillin in cerebrospinal fluid. Brit. med. J. 283:646, 1981.

[15] 15. EKBOM, K. - Carbamazepine in the treament of tabetic lightning pains. Arch. Neurol. (Chicago) 15:374, 1972.

[16] 16. FLETCHER, W.A. & SHARPE, J.A. - Tonic pupils in neurosyphilis. Neurology 36:188, 1986.

[17] 17. FORD, W.T. ; WIGALL, R.H. & STOKES, J.H. - Penicillin therapy of assymptomatic neurosyphilis: the spinal fluid cell count as a guide to therapeutic response and re-treament. Arch. int. Med. 88:235, 1951.

[18] 18. FOURNIER, A. - Leçons sur la Période Praeataxique du Tabes d'Origine Syphilitique. Masson, Paris, 1885.

[19] 19. GIMENEZ-ROLDAN, S. & MARTIN, M. - Tabetic lightning pains : high-dose intravenous penicillin versus carbamazepine therapy. Europ. Neurol. 20:424, 1981.

[20] 20. GREENE, B.M. ; MILLER, N.R. & BINUM, T.E. - Failure of penicillin G benzathine in the treatment of neurosyphilis. Arch. int. Med. 98:1117, 1980.

[21] 21. HAHN, R.D. - Some remarks on management of neurosyphilis. J. chronic Dis. 13:1, 1961.

[22] 22. HOOSHMAND, H. - Tabetic lightning pains. Arch. Neurol. (Chicago) 28:70, 1973.

[23] 23. HOOSHMAND, H. ; ESCOBAR, M.R. & KOPF, S.W. - Neuro-syphilis : a study of 241 patients. J. amer. med. Assoc. 219:726, 1972.

[24] 24. KOTEEN, H. ; DOTY, E. J. ; WEBSTER, B. & McDERMOTT, W. - Penicillin therapy in neurosyphilis. Amer. J. Syph. 31:1, 1947.

[25] 25. LANIGAN-O'KEEFFEE, F.M. - Return to normal of Argyll Robertson pupils after treatment. Brit. med. J. 2:1191, 1977.

[26] 26. LOWHAGEN, G.B. ; BRORSON, J.E. & KAIJSER, B. - Penicillin concentrations in cerebrospinal fluid and serum after intramuscular, intravenous and oral administration to syphilis patients. Acta derm-venereol. (Stockholm) 63:53, 1983.

[27] 27. LUXON, L.M. - Neurosyphilis. Internat. J. Derm. 19:310, 1980.

[28] 28. MAPELLI, G. - Must we revise our clinical concepts of tabetic neurosyphilis? Acta neurol. belg. 81:12, 1981.

[29] 29. MARTIN MORO, M.; BARTOLOME, P.; ANDRES, C. ; NUNEZ, A.G. ; MATEO, O. ; VILLANUEVA, J.A. & GIMENEZ-ROLDAN, S. - Penicilina intravenosa en el tratamiento de la neurosifilis. Arch. Neurobiol. (Madrid) 45:29, 1982.

[30] 30. MICHEL, D.; BLANC, A.; LAURENT, B. ; FOYATIER, N. & PORTFAIX, M. - Etude biologique, psychométrique et tomodensimétrique de la neurosyphilis traitée. Rev. neurol. (Paris) 139:737, 1983.

[31] 31. MOHR, J.A. ; GRIFFITHS, W. ; JACKSON, R. ; S A AD AH, H.; BIRD, P. & RIDDLE, J. - Neurosyphilis and penicillin levels in cerebrospinal fluid. J. amer. med. Assoc. 236:2208, 1976.

[32] 32. NITRINI, R. - (a) Neurossífilis : análise de alguns aspectos clínicos e laboratoriais. Tese, São Paulo, 1981. (b) Neurossífilis: penicilinoterapia intravenosa em altas doses. Tese. São Paulo, 1986.

[33] 33. N1TRINI. R.; BACHESCHI, L.A.; NÓBREGA, J.P.S.; SCAFF, M. & YASUDA, N. - Neurossífilis resistente a altas doses de penicilina: registro de um caso. Arq. Neuro-Psiquiat. (São Paulo) 42:55, 1984.

[34] 34. ORBAN, T. - Experience with a follow-up examination of 200 tabetic patients. Acta psychiat. scand. 32:89, 1957.

[35] ³⁵
ORGANIZAÇÃO MUNDIAL DE SAÚDE - Treponemal infections: report of a WHO scientific group. World Health Organization, Geneva, 1982.

[36] 36. OSELKA, G.W.; LEVI, G.C.: LOPES, H.V.; MENDONÇA, J.S.; BALDY, J.L.S.; TRABULSI, L.R. & AMATO NETO, V. - Antibióticos na Prática Médica. Gremed, São Paulo, 1978.

[37] 37. POLNIKORN, N.; WITOONPANICH, R.; VORACII1T, M.; VEJJAJIVA, S. & VEJJAJIVA, A. - Penicillin concentrations in the cerebrospinal fluid after benzathine penicillin and probenecid in the treatment of syphilis. Brit. J. vener. Dis. 58:342, 1982.

[38] 38. POLNIKORN, N.: WITOONPANICH, R.; VORACHIT, M.; VEJJAJIVA, S. & VEJJAJIVA, A. - Penicillin concentrations in cerebrospinal fluid after different treatment regimens for syphilis. Brit. J. vener. Dis. 56:363, 1980.

[39] 39. REIN, M.F. - Treatment of neurosyphilis. J. amer. med. Assoc. 246:2613, 1981.

[40] 40. RICE, N.S.C.; DUNLOP, E.M.C.; JONES, B.R.; HARE, M. J.; KING, A.J.; RODIN, P.; MUSHIN, A. & WILKINSON. A.E. - Demonstration of treponema-like forms in cases of treated and untreated late syphilis and of treated early syphilis. Brit. J. vener. Dis. 46:1, 1970.

[41] 41. ROMANOWSHI, B.: STARREVELD. E. & JAREMA, A.J. - Treatment of neurosyphilis with chloramphenicol: a case report. Brit. J. vener. Dis. 59:225, 1983.

[42] 42. ROSE. A.S. & SOLOMON. H.C. - Penicillin in the treatment of neurosyphilis. J. amer. med. Assoc. 133:5. 1947.

[43] 43. SCHMIDT. R.P. & GONYEA, E.F. - Neurosyphilis. In: A.B. Baker & R.J. Joynt - Clinical Neurology. Harper and Row, Philadelphia, 1980.

[44] 44. SEGAL, P.; JANISZEWSKA-GELDNER, B. & LEONOW1CZ-MICHNIOWSKA, J. - Results of penicillin therapy in syphilitic primary optic atrophy. Brit. J. vener. Dis. 36:257, 1960.

[45] 45. SIMON. R.P. - Neurosyphilis. Arch. Neurol. (Chicago) 42:606, 1985.

[46] 46. STOCKLI, H.R.; FOLLATH, F.: PROBST, A. & RUFLI, T. - Theraoieversager bei Neurolues (Falbericht) und Penicillinversagen im Liquor cerebrospinalis. Schweiz. Rdsch. med. Prax. 74:885, 1985.

[47] 47. TRAMONT. E.C. - Persistence of Treponema pallidum following; penicillin G therapy. J. amer. med. Assoc. 236:2206, 1976.

[48] 48. WEINSTEIN, J.M.; LEXOW, S.S.: HO, P. & SPICKARDS, A. - Acute syphilitic optic neuritis. Arch. Ophthal. 99:1392, 1981.

[49] 49. WILNER, E. & BRODY, J.A. - Prognosis of general paresis after treatment. Lancet 2:1370, 1968.

[50] 50. YOBS. A.R.: CLARK JR.. J.W.: MOTHERSHED, S.E.; BULLARD, J.C. & ARTLEY, C.W. - Further observations on the persistence of Treponema pallidum after treatment in rabbits and humans. Brit. J. vener. Dis. 44:116, 1968.

[51] 51. YODER, F.W. - Penicillin treatment of neurosyphilis: are recommended dosages sufficient? J. amer. med. Assoc. 232:270, 1975.

[52] 52. ZUKERMAN, E.; CARDOSO, W.; Di MIGUELI, H.; REIS FILHO, I.; SCHWARTZMAN, J.S.: BEI. A.; MOREIRA, M.H.; GIORGI, D.R.; ROTBERG, A. & REIS, J.B. - Incidência da neurossífilis * de sua» formas clínicas em São Paulo. Rev. paul. Med. 70:270, 1967.