Discrepancy, coincidence or evidence in chronic idiopathic spastic paraparesis throughout the world: a meta-analysis on 2811 patients

Leon-S, Fidias E.; Costa, Carlos Mauricio de Castro; Gaffga, Nicholas

doi:10.1590/S0004-282X1997000400002

Abstracts

HTLV-I has been associated with a chronic idiopatic spastic paraparesis (CHISPA) in man; however, a complete understanding of this association is still debated. We selected the most comprehensible papers on this topic between 1985 and 1996, and found that 1261 out of 2811 patients (44.9%) reported, throughout the world, were HTLV-I positive. The mean age was 39.5 years and there was a female predominance of 1.9:1. These results do not exclude the causality of HTLV-I as a germen associated to CHISPA; however, other causes (e.g., toxic, immunosuppressors) must be considered as participating in the multistep neurodegeneration observed in CHISPA throughout the world.

HTLV-I; spastic paraparesis; meta-analysis; retrovirus; environmental cofactors

O retrovirus HTLV-1 tem sido associado a paraparesia espástica idiopática crônica (PEIC) no homem; contudo uma compreensão completa dessa associação é motivo de debate. Selecionamos os estudos mundiais mais expressivos sobre esse assunto no período de 1985 a 1996 e verificamos que 1261 dos 2811 (44,9%) dos pacientes relatados eram HTLV-1 positivos. A média de idade era de 39,5 anos com predomínio feminino de 1,9:1. Estes resultados não excluem a causalidade do HTLV-1 como um germe associado a PEIC em todo o mundo.

HTLV-I; paraparesia espástica; meta-análise; retrovirus; cofatores ambientais

Discrepancy, coincidence or evidence in chronic idiopathic spastic paraparesis throughout the world: a meta-analysis on 2811 patients

Discrepância, coincidência ou evidência em paraparesia espástica idiopática crônica no mundo: uma meta-análise de 2811 pacientes

Fidias E. Leon-S^I; Carlos Mauricio de Castro Costa^II; Nicholas Gaffga^III

^IMD, PhD, FUAB, Laboratory of Clinical Neurophysiology and Human Neurobiology, Unit of Neurology, UIS-Santander University School of Medicine Bucaramanga, Colombia

^IIMD, PhD, Departamento de Fisiologia e Farmacologia (Laboratório de Neurologia Experimental) e Serviço de Neurologia-HUWC (UFCE). [Caixa Postal 3157 - 60430-160 Fortaleza CE - Brasil]

^IIIUnit of International Research, Department of Public Health, University of Alabama at Birmingham, AL, USA. Aceite: 15-maio-1997

ABSTRACT

HTLV-I has been associated with a chronic idiopatic spastic paraparesis (CHISPA) in man; however, a complete understanding of this association is still debated. We selected the most comprehensible papers on this topic between 1985 and 1996, and found that 1261 out of 2811 patients (44.9%) reported, throughout the world, were HTLV-I positive. The mean age was 39.5 years and there was a female predominance of 1.9:1. These results do not exclude the causality of HTLV-I as a germen associated to CHISPA; however, other causes (e.g., toxic, immunosuppressors) must be considered as participating in the multistep neurodegeneration observed in CHISPA throughout the world.

Key-words: HTLV-I, spastic paraparesis, meta-analysis, retrovirus, environmental cofactors.

RESUMO

O retrovirus HTLV-1 tem sido associado a paraparesia espástica idiopática crônica (PEIC) no homem; contudo uma compreensão completa dessa associação é motivo de debate. Selecionamos os estudos mundiais mais expressivos sobre esse assunto no período de 1985 a 1996 e verificamos que 1261 dos 2811 (44,9%) dos pacientes relatados eram HTLV-1 positivos. A média de idade era de 39,5 anos com predomínio feminino de 1,9:1. Estes resultados não excluem a causalidade do HTLV-1 como um germe associado a PEIC em todo o mundo.

Palavras-chave: HTLV-I, paraparesia espástica, meta-análise, retrovirus, cofatores ambientais.

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1. Araújo AQ-C, Alfonso CR, Schor D. Clinical and demographic features of HTLV-I associated myelopathy /tropical spastic paraparesis (HAM/TSP) in Rio de Janeiro, Brasil. Acta Neurol Scand 1993;88:59-62.
2. Bazarbachi A, Soriano V, Vallejo A. Mycosis fungoides and Sezary syndrome are not associated with HTLV-I infection:an international study. J AIDS Hum Retrov 1995; 10:237.
3. Bhigjee AI, Bill PL, Hammond MG. HLA profile and HTLV-I associated myelopathy(HAM/TSP) in Natal. South Africa. J Neurol Neurosurg Psychiatry 1991;55:329-330.
4. Carrier L, Verdugo R, Vergara C. Paraparesia esporádica del adulto por degenracion retrograda del sistema piramidal. Neurol Col 1983;7:103-112.
5. Cook GC. Cause of AIDS. BMJ 1996;312:1231.
6. Cosnett JE. Unexplained spastic myelopathy:41 cases in a non-European hospital. South Af Med J 1965;39:592-595.
7. Cruickshank JK, Corbin DOC, Bucher B. HTLV-I and neurological disease. In Rudge P (ed). Bailliere's clinical neurology: neurological aspects of human retrovirus, vol 1. London: Bailliere Tindall 1992:61-81.
8. De Castro Costa CM. A review of tropical spastic paraparesis in Ceará (northeastern Brasil). In Zaninivic V (ed). HTLV-I: trusths and questions. Cali: Feriva, 1996:105-130.
9. De Castro Costa CM, Carton H, Goubau P, D'Almeida JAC. Brazilian studies on tropical spastic paraparesis. Arq Neuropsiquiatr 1994;52:585-591.
10. De-The G, Giordano C, Gessain A. Human retroviruses HTLV-I, HIV, and HIV 2 and neurological diseases in some equatorial areas of Africa. J AIDS 1989;2:550-556.
11. Dominguez RB, Muniz MR, Pinho JRR. Human T lymphotropic virus type I associated myelopathy/tropical spastic paraparesis in São Paulo, Brasil. Clin Inf Dis 1995;20:1540-1542.
12. Garcia-Vallejo F, Rengifo B, Essex M. Nucleotide sequence variation in the envelope of patients with tropical spastic paraparesis/human T-cell leukemia virus type I associated myelopathy. J AIDS Human Retroviral 1995;10:283.
13. Gessain A, Barin F, Vernant JC. Antibodies to human T-lymphotropic virus type I in patients with tropical spastic paraparesis. Lancet 1985;2:407-409.
14. Gessain A, Gout O, Saal F. Epidemiology and immunovirology of human T-cell leukemia/lymphoma virus type I-associated adult T-cell leukemia and chronic myelopathies as seen in France. Cancer Res 1990;50:5692s-5696s.
15. Gracia F, Castillo LC, Larreategui M. Relation between human T-lymphotropic virus type I and neurological diseases in Panama: 1985-1990. J AIDS Hum Retroviral 1995;10:192-197.
16. Jogcsar VB, De Bruyn CC, Bhigjee AI. Adult T-cell leukemia/lymphoma associated with HTLV-I in Natal. South Af Med J 1992;81:528-529.
17. Kayembe K, Goubau P, Demyter J. A cluster of HTLV-I associated tropical spastic paraparesis in Equator (Zaire): ethnic and familiar distribution. J Neurol Neurosurg Psychiatry 1990;53:4-10.
18. Kawano F, Tsuda H, Yamaguchi K. Unusual clinical courses of adult T-cell leukemia in siblings. Cancer 1984;54:131-134.
19. Kuroda Y, Yukitake M, Kurohara K. A follow-up on spastic paraparesis in Japanese HAM/TSP. J Neurol Sci 1995;132:174-176.
20. Leon-S FE. Salmon, ventilation and mycotoxin inhalation. Lancet 1995;346:1707.
21. Leon-S FE. Kuru, volcanes y virus lentos:no es la cancion, es el cantante. Actual Biom Col 1995;2:81-84.
22. Leon-S FE. Nutritional rehabilitation in tropical neurology In Chopra JS, Sawhney IMS (eds). Tropical neurology. London: Churchill Livingstone, in press.
23. Leon-S FE, Arimura K, Arimura Y. Clinical neurophysiological comparative study of HAM/TSP. Arch Med Res 1995;26:397-403.
24. Leon-S FE, Arimura K, Osame M. Multiple sclerosis and HTLV-I associated myelopathy/tropical spastic paraparesis are two distinct clinical entities. Multiple Sclerosis 1996;2:88-90.
25. Leon-S FE, Ariza De-Leon A, Ariza-C A, Leon-S ME. Mitochondrial DNA and some more on the Japanese-South American linkage. South Pac Study 1994;9:9-15.
26. Leon-S FE, Ariza-Deleon A, Ariza-C A, Leon ME. Peopling the Americas. Science 1996;273:723-724.
27. Leon-S FE, Carpintero M, DeMerino NV. Meteorological conditions in HAM/TSP:coincidence or clue?. Rev Med Chile: in press.
28. Leon-S FE, Carpintero M, Gaffa N, Ocampo L, Bayona J. Mycotoxins in myelopathies of man. Lancet 1996:348:1039.
29. Leon-S FE, Zaninovic V. Clima, cultura y cofactores en el HAM/TSP en Colombia. Acta Med Col 1994; 19:248.
30. Leon-S FE, Zaninovic V. Geographical consideration on HAM/TSP in Japan. Rev Inst Med Trap Sao Paulo 1995;37:185-186.
31. Leon-S FE, Zaninovic V. Hechos, factores y cofactores en el camino de los retrovirus. Médicas UIS 1995;9:68-72.
32. Mani KS, Mani AJ, Montgomery D. A spatic paraplegic syndrome in South India. J Neurol Sci 1969;9:179-199.
33. Monique B, Daniel M, Bernard G. Distribution of HLA class I and class II loci in a chreole population from Caribbean basin, infected by HTLV-I. Hum Immunol 1996;47:121.
34. Molgaard CA, Eisenman PA, Ryden LA, Golbeck AL. Neuroepidemiology of human T-lymphotrophic virus tipe-I-associated tropical spastic paraparesis. Neuroepidemiology 1989;8:109-123.
35. Nakagawa M, Izumo S, Ijichi S. HTLV-I associated myelopathy: analysis of 213 patients based on clinical features and laboratory findings. J Neurovirol 1995;1:50-61.
36. Nagai H, Kinoshita T, Imamura J. Genetic alteration of p53 in some patients with adult T cell leukemia. Jpn J Cancer Res 1991;82:1421-1427.
37. Nishimura S, Asou N, Suzushima H. p53 gene mutation and loss of heterozygosity are associated with increased risk of disease progression in adult T cell leukemia. Leukemia 1995;9:598-604.
38. Osame M, Igata A, Matsumoto M. HTLV-I-associated myelopathy (HAM), treatment trials, retrospective survey and clinical and laboratory findings. Hematol Rev 1990;3:271-284.
39. Osame M, Usuku K, Izumo S. HTLV-I associated myelopathy: a new clinical entity. Lancet 1986;1 :1031-1032.
40. Pancake BA, Zucker-Franklin D, Coutava SEE. The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell Iymphotropic virus associated disease: a study of 50 patients. J Clin Invest 1995;95:547-554.
41. Poiez BJ, Ruscetti FW, Gazdar AF. Detection and isolation of type-C retrovirus particles from fresh and cultured lymphocites of a patient with cutaneous T cell-lymphoma. Proc Natl Acad Sci USA 1980;77:7415-7419.
42. Pombo de Oliveira MS, Matutes E, Schulz T, Carvalho SM. T-cell malignancies in Brazil. Clinico-pathological and molecular studies of HTLV-I-positive and -negative cases. Int J Cancer 1995;60:823-827.
43. Rodgers-Johnson P, Gadjusek DC, Morgan OS. HTLV-I and HTLV-III antibodies and tropical spastic paraparesis. Lancet 1985;2:1247-1248.
44. Roman G, Osame M. Identity of HTLV-I associated tropical spastic paraparesis and HTLV-I associated myelopathy. Lancet 1988;1:651.
45. Roman G, Spencer P, Schoemberg B. Tropical myeloneuropathies: the hidden endemies. Neurology 1985;35:1158-1170.
46. Rudge P, Ali A, Cruickshank JK. Multiple sclerosis, tropical spastic paraparesis and HTLV-1D infection in Afro-Caribbean patients in the United Kingdom. J Neurol, Neurosurg Psychiatry 1991;54:689-694.
47. Sakashita A, Hattori T, Miller CW et al. Mutations of the p53 gene in adult T-cell leukemia. Blood 1992;79:477-480.
48. Shimoyama M. Human T-cell leukemia virus type I (HTLV-I) negative adult T-cell leukemia/lymphoma. Hem Rev 1990;3:211-222.
49. Singhal B, Lalkaka JA, Ladiwala U. Tropical spastic paraparesis in India. In Zaninovic V (ed). HTLV-1: thrusts and questions 1996:159-165.
50. Sonoda S, Yashiki S, Kuwayama M et al. HLA and HTLV: workshop report. Hum Immunol 1996;47:120.
51. Strachan H. On a form of multiple neuritis prevalent in the West Indies. Practitioner 1897;59:477-484.
52. Tajima K, Hinuma Y. Epidemiology of HTLV-I/II in Japan and the world. Gann Monog Cancer Res 1992;39:129-149.
53. Takatsuki K. Adult T-cell leukemia (ATL): an overview. In Roman GC, Vernant JC, Osame M(eds). HTLV-I and the nervous system. New York: Alan R Liss, 1989:57-63.
54. Takatsuki K, Uchiyama T, Sagawa K. Adult T-cell leukemia in Japan. In Seno S, Takaku F, Irino S (eds). Topics in hematology. Amsterdam: Excerpta Medica, 1977:73-77.
55. Takesaki T, Tajima K. Epidemiology of ATLL and HAM/TSP in Asia. In Zaninovic V(ed). HTLV-I: thrusts and questions. Cali: Feriva 1996:66-77.
56. Tamiya S, Matsuoka M;Takemoto S. Adult T cell leukemia following HTLV-I associated myelopathy/tropical spastic paraparesis: case reports and implication to the natural course of ATL. Leukemia 1995;9:1768-1770.
57. Terada K, Katamine S, Eguchi K. Prevalence of serum and salivary antibodies to HTLV-I in Sjogren's syndrome. Lancet 1994;344:1116-1119.
58. Trelles L. Tropical spastic paraparesis in Peru. In Roman GC, Vernant JC, Osame M(eds). HTLV-1 and the nervous system. New York: Alan R liss, 1989:157-165.
59. Tylleskar T, Banea M, Bikangi N et al. Dietary determinants of a non-progressive spastic paraparesis(Konzo): a case-referent study in a high incidence area of Zaire. Int J Epidemiol 1995;24:949-956.
60. Xu X, Heidenreich O, Nerenberg M. Role of kinases in HTLV-I transformation. J Invest Med 1996;44:113-123.
61. Zaninovic V. Paraparesia espastica tropical en Colombia. In Zaninovic V, Gallindo J, Blank A (eds). Enfermedades asociadas con el HTLV-I. Cali: XYZ, 1992:77-86.
62. Zaninovic V (ed). HTLV-I: thrusts and questions. Cali: Feriva, 1996.
63. Zaninovic V, Biojo R, Arango C et al. Asociacion entre la infección por el virus linfotropico tipo I ( HTLV-I ) y la paraparesia espastica del Pacifico. Col Med 1986;17:101-103.
64. Zaninovic V, Biojo R, Barreto P. Paraparesia espastica del Pacifico. Col Med 1981; 12:111 -117.
65. Zaninovic V, Leon-S FE. Fifteen years of follow-up on HTLV-I positive and HTLV-I negative spastic paraparesis in Southwestern Colombia. J Neurovirol 1996;2:357-360.

Publication Dates

Publication in this collection
18 Oct 2010
Date of issue
Sept 1997

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

[1] 1. Araújo AQ-C, Alfonso CR, Schor D. Clinical and demographic features of HTLV-I associated myelopathy /tropical spastic paraparesis (HAM/TSP) in Rio de Janeiro, Brasil. Acta Neurol Scand 1993;88:59-62.

[2] 2. Bazarbachi A, Soriano V, Vallejo A. Mycosis fungoides and Sezary syndrome are not associated with HTLV-I infection:an international study. J AIDS Hum Retrov 1995; 10:237.

[3] 3. Bhigjee AI, Bill PL, Hammond MG. HLA profile and HTLV-I associated myelopathy(HAM/TSP) in Natal. South Africa. J Neurol Neurosurg Psychiatry 1991;55:329-330.

[4] 4. Carrier L, Verdugo R, Vergara C. Paraparesia esporádica del adulto por degenracion retrograda del sistema piramidal. Neurol Col 1983;7:103-112.

[5] 5. Cook GC. Cause of AIDS. BMJ 1996;312:1231.

[6] 6. Cosnett JE. Unexplained spastic myelopathy:41 cases in a non-European hospital. South Af Med J 1965;39:592-595.

[7] 7. Cruickshank JK, Corbin DOC, Bucher B. HTLV-I and neurological disease. In Rudge P (ed). Bailliere's clinical neurology: neurological aspects of human retrovirus, vol 1. London: Bailliere Tindall 1992:61-81.

[8] 8. De Castro Costa CM. A review of tropical spastic paraparesis in Ceará (northeastern Brasil). In Zaninivic V (ed). HTLV-I: trusths and questions. Cali: Feriva, 1996:105-130.

[9] 9. De Castro Costa CM, Carton H, Goubau P, D'Almeida JAC. Brazilian studies on tropical spastic paraparesis. Arq Neuropsiquiatr 1994;52:585-591.

[10] 10. De-The G, Giordano C, Gessain A. Human retroviruses HTLV-I, HIV, and HIV 2 and neurological diseases in some equatorial areas of Africa. J AIDS 1989;2:550-556.

[11] 11. Dominguez RB, Muniz MR, Pinho JRR. Human T lymphotropic virus type I associated myelopathy/tropical spastic paraparesis in São Paulo, Brasil. Clin Inf Dis 1995;20:1540-1542.

[12] 12. Garcia-Vallejo F, Rengifo B, Essex M. Nucleotide sequence variation in the envelope of patients with tropical spastic paraparesis/human T-cell leukemia virus type I associated myelopathy. J AIDS Human Retroviral 1995;10:283.

[13] 13. Gessain A, Barin F, Vernant JC. Antibodies to human T-lymphotropic virus type I in patients with tropical spastic paraparesis. Lancet 1985;2:407-409.

[14] 14. Gessain A, Gout O, Saal F. Epidemiology and immunovirology of human T-cell leukemia/lymphoma virus type I-associated adult T-cell leukemia and chronic myelopathies as seen in France. Cancer Res 1990;50:5692s-5696s.

[15] 15. Gracia F, Castillo LC, Larreategui M. Relation between human T-lymphotropic virus type I and neurological diseases in Panama: 1985-1990. J AIDS Hum Retroviral 1995;10:192-197.

[16] 16. Jogcsar VB, De Bruyn CC, Bhigjee AI. Adult T-cell leukemia/lymphoma associated with HTLV-I in Natal. South Af Med J 1992;81:528-529.

[17] 17. Kayembe K, Goubau P, Demyter J. A cluster of HTLV-I associated tropical spastic paraparesis in Equator (Zaire): ethnic and familiar distribution. J Neurol Neurosurg Psychiatry 1990;53:4-10.

[18] 18. Kawano F, Tsuda H, Yamaguchi K. Unusual clinical courses of adult T-cell leukemia in siblings. Cancer 1984;54:131-134.

[19] 19. Kuroda Y, Yukitake M, Kurohara K. A follow-up on spastic paraparesis in Japanese HAM/TSP. J Neurol Sci 1995;132:174-176.

[20] 20. Leon-S FE. Salmon, ventilation and mycotoxin inhalation. Lancet 1995;346:1707.

[21] 21. Leon-S FE. Kuru, volcanes y virus lentos:no es la cancion, es el cantante. Actual Biom Col 1995;2:81-84.

[22] 22. Leon-S FE. Nutritional rehabilitation in tropical neurology In Chopra JS, Sawhney IMS (eds). Tropical neurology. London: Churchill Livingstone, in press.

[23] 23. Leon-S FE, Arimura K, Arimura Y. Clinical neurophysiological comparative study of HAM/TSP. Arch Med Res 1995;26:397-403.

[24] 24. Leon-S FE, Arimura K, Osame M. Multiple sclerosis and HTLV-I associated myelopathy/tropical spastic paraparesis are two distinct clinical entities. Multiple Sclerosis 1996;2:88-90.

[25] 25. Leon-S FE, Ariza De-Leon A, Ariza-C A, Leon-S ME. Mitochondrial DNA and some more on the Japanese-South American linkage. South Pac Study 1994;9:9-15.

[26] 26. Leon-S FE, Ariza-Deleon A, Ariza-C A, Leon ME. Peopling the Americas. Science 1996;273:723-724.

[27] 27. Leon-S FE, Carpintero M, DeMerino NV. Meteorological conditions in HAM/TSP:coincidence or clue?. Rev Med Chile: in press.

[28] 28. Leon-S FE, Carpintero M, Gaffa N, Ocampo L, Bayona J. Mycotoxins in myelopathies of man. Lancet 1996:348:1039.

[29] 29. Leon-S FE, Zaninovic V. Clima, cultura y cofactores en el HAM/TSP en Colombia. Acta Med Col 1994; 19:248.

[30] 30. Leon-S FE, Zaninovic V. Geographical consideration on HAM/TSP in Japan. Rev Inst Med Trap Sao Paulo 1995;37:185-186.

[31] 31. Leon-S FE, Zaninovic V. Hechos, factores y cofactores en el camino de los retrovirus. Médicas UIS 1995;9:68-72.

[32] 32. Mani KS, Mani AJ, Montgomery D. A spatic paraplegic syndrome in South India. J Neurol Sci 1969;9:179-199.

[33] 33. Monique B, Daniel M, Bernard G. Distribution of HLA class I and class II loci in a chreole population from Caribbean basin, infected by HTLV-I. Hum Immunol 1996;47:121.

[34] 34. Molgaard CA, Eisenman PA, Ryden LA, Golbeck AL. Neuroepidemiology of human T-lymphotrophic virus tipe-I-associated tropical spastic paraparesis. Neuroepidemiology 1989;8:109-123.

[35] 35. Nakagawa M, Izumo S, Ijichi S. HTLV-I associated myelopathy: analysis of 213 patients based on clinical features and laboratory findings. J Neurovirol 1995;1:50-61.

[36] 36. Nagai H, Kinoshita T, Imamura J. Genetic alteration of p53 in some patients with adult T cell leukemia. Jpn J Cancer Res 1991;82:1421-1427.

[37] 37. Nishimura S, Asou N, Suzushima H. p53 gene mutation and loss of heterozygosity are associated with increased risk of disease progression in adult T cell leukemia. Leukemia 1995;9:598-604.

[38] 38. Osame M, Igata A, Matsumoto M. HTLV-I-associated myelopathy (HAM), treatment trials, retrospective survey and clinical and laboratory findings. Hematol Rev 1990;3:271-284.

[39] 39. Osame M, Usuku K, Izumo S. HTLV-I associated myelopathy: a new clinical entity. Lancet 1986;1 :1031-1032.

[40] 40. Pancake BA, Zucker-Franklin D, Coutava SEE. The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell Iymphotropic virus associated disease: a study of 50 patients. J Clin Invest 1995;95:547-554.

[41] 41. Poiez BJ, Ruscetti FW, Gazdar AF. Detection and isolation of type-C retrovirus particles from fresh and cultured lymphocites of a patient with cutaneous T cell-lymphoma. Proc Natl Acad Sci USA 1980;77:7415-7419.

[42] 42. Pombo de Oliveira MS, Matutes E, Schulz T, Carvalho SM. T-cell malignancies in Brazil. Clinico-pathological and molecular studies of HTLV-I-positive and -negative cases. Int J Cancer 1995;60:823-827.

[43] 43. Rodgers-Johnson P, Gadjusek DC, Morgan OS. HTLV-I and HTLV-III antibodies and tropical spastic paraparesis. Lancet 1985;2:1247-1248.

[44] 44. Roman G, Osame M. Identity of HTLV-I associated tropical spastic paraparesis and HTLV-I associated myelopathy. Lancet 1988;1:651.

[45] 45. Roman G, Spencer P, Schoemberg B. Tropical myeloneuropathies: the hidden endemies. Neurology 1985;35:1158-1170.

[46] 46. Rudge P, Ali A, Cruickshank JK. Multiple sclerosis, tropical spastic paraparesis and HTLV-1D infection in Afro-Caribbean patients in the United Kingdom. J Neurol, Neurosurg Psychiatry 1991;54:689-694.

[47] 47. Sakashita A, Hattori T, Miller CW et al. Mutations of the p53 gene in adult T-cell leukemia. Blood 1992;79:477-480.

[48] 48. Shimoyama M. Human T-cell leukemia virus type I (HTLV-I) negative adult T-cell leukemia/lymphoma. Hem Rev 1990;3:211-222.

[49] 49. Singhal B, Lalkaka JA, Ladiwala U. Tropical spastic paraparesis in India. In Zaninovic V (ed). HTLV-1: thrusts and questions 1996:159-165.

[50] 50. Sonoda S, Yashiki S, Kuwayama M et al. HLA and HTLV: workshop report. Hum Immunol 1996;47:120.

[51] 51. Strachan H. On a form of multiple neuritis prevalent in the West Indies. Practitioner 1897;59:477-484.

[52] 52. Tajima K, Hinuma Y. Epidemiology of HTLV-I/II in Japan and the world. Gann Monog Cancer Res 1992;39:129-149.

[53] 53. Takatsuki K. Adult T-cell leukemia (ATL): an overview. In Roman GC, Vernant JC, Osame M(eds). HTLV-I and the nervous system. New York: Alan R Liss, 1989:57-63.

[54] 54. Takatsuki K, Uchiyama T, Sagawa K. Adult T-cell leukemia in Japan. In Seno S, Takaku F, Irino S (eds). Topics in hematology. Amsterdam: Excerpta Medica, 1977:73-77.

[55] 55. Takesaki T, Tajima K. Epidemiology of ATLL and HAM/TSP in Asia. In Zaninovic V(ed). HTLV-I: thrusts and questions. Cali: Feriva 1996:66-77.

[56] 56. Tamiya S, Matsuoka M;Takemoto S. Adult T cell leukemia following HTLV-I associated myelopathy/tropical spastic paraparesis: case reports and implication to the natural course of ATL. Leukemia 1995;9:1768-1770.

[57] 57. Terada K, Katamine S, Eguchi K. Prevalence of serum and salivary antibodies to HTLV-I in Sjogren's syndrome. Lancet 1994;344:1116-1119.

[58] 58. Trelles L. Tropical spastic paraparesis in Peru. In Roman GC, Vernant JC, Osame M(eds). HTLV-1 and the nervous system. New York: Alan R liss, 1989:157-165.

[59] 59. Tylleskar T, Banea M, Bikangi N et al. Dietary determinants of a non-progressive spastic paraparesis(Konzo): a case-referent study in a high incidence area of Zaire. Int J Epidemiol 1995;24:949-956.

[60] 60. Xu X, Heidenreich O, Nerenberg M. Role of kinases in HTLV-I transformation. J Invest Med 1996;44:113-123.

[61] 61. Zaninovic V. Paraparesia espastica tropical en Colombia. In Zaninovic V, Gallindo J, Blank A (eds). Enfermedades asociadas con el HTLV-I. Cali: XYZ, 1992:77-86.

[62] 62. Zaninovic V (ed). HTLV-I: thrusts and questions. Cali: Feriva, 1996.

[63] 63. Zaninovic V, Biojo R, Arango C et al. Asociacion entre la infección por el virus linfotropico tipo I ( HTLV-I ) y la paraparesia espastica del Pacifico. Col Med 1986;17:101-103.

[64] 64. Zaninovic V, Biojo R, Barreto P. Paraparesia espastica del Pacifico. Col Med 1981; 12:111 -117.

[65] 65. Zaninovic V, Leon-S FE. Fifteen years of follow-up on HTLV-I positive and HTLV-I negative spastic paraparesis in Southwestern Colombia. J Neurovirol 1996;2:357-360.