The value of csf analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis

Puccioni-Sohler, Marzia; Kitze, Bernd; Felgenhauer, Klaus; Graef, Iris T.; Lange, Peter; Novis, Sergio; Reiber, Hansotto; Vaz, Beatriz

doi:10.1590/S0004-282X1995000500008

Abstracts

Cerebrospinal fluid (CSF) and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/ tropical spastic paraparesis), six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control) from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA). All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG). In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response) were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono- and polyspecific immune responses is discussed for these chronic neurological diseases.

HTLV-I; HAM/TSP; cerebrospinal fluid; antibody index

Amostras de líquido cefalorraquidiano (LCR) e soro de 17 pacientes brasileiros com HAM/TSP, seis com esclerose múltipla e seis com epilepsia idiopática (controle não-inflamatório) foram analisadas para a presença de anticorpos para os vírus do sarampo, rubéola, varicela zoster e herpes simples pelo método de ELISA. Todos os casos de HAM/TSP e esclerose múltipla tinham resposta imune intratecal (IgG oligoclonal). Somente 1/17 casos de HAM/TSP apresentavam resposta imune poliespecifica intratecal para sarampo e rubéola. Anticorpos específicos para sarampo e rubeola (resposta MRZ) foram observados em todos os pacientes com esclerose múltipla, mas não nos controles com epilepsia idiopática. A relevância das respostas poliespecifica e monoespecifica é discutida para essas doenças neurológicas crônicas.

HTLV-I; HAM/TSP; líquido cefalorraquidiano; índice de anticorpos

The value of csf analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis

Valor da análise do LCR para o diagnóstico diferencial de mielopatia associada ao HTLV-I e esclerose múltipla

Marzia Puccioni-Sohler^{I, II, III}; Bernd Kitze^I; Klaus Felgenhauer^I; Iris T.Graef^I; Peter Lange^I; Sergio Novis^II; Hansotto Reiber^I; Beatriz Vaz^II

^INeurochemistry Labor - Klinik und Poliklinik für Neurologie der Georg-August-Universität Göttingen, Germany

^IIServiço de Neurologia, Universidade Federal do Rio de Janeiro (HUCFF/UFRJ), Brazil

^IIIFellowship from DAAD and CNPq/CAPES

SUMMARY

Cerebrospinal fluid (CSF) and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/ tropical spastic paraparesis), six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control) from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA). All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG). In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response) were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono- and polyspecific immune responses is discussed for these chronic neurological diseases.

Key words:HTLV-I, HAM/TSP, cerebrospinal fluid, antibody index

RESUMO

Amostras de líquido cefalorraquidiano (LCR) e soro de 17 pacientes brasileiros com HAM/TSP, seis com esclerose múltipla e seis com epilepsia idiopática (controle não-inflamatório) foram analisadas para a presença de anticorpos para os vírus do sarampo, rubéola, varicela zoster e herpes simples pelo método de ELISA. Todos os casos de HAM/TSP e esclerose múltipla tinham resposta imune intratecal (IgG oligoclonal). Somente 1/17 casos de HAM/TSP apresentavam resposta imune poliespecifica intratecal para sarampo e rubéola. Anticorpos específicos para sarampo e rubeola (resposta MRZ) foram observados em todos os pacientes com esclerose múltipla, mas não nos controles com epilepsia idiopática. A relevância das respostas poliespecifica e monoespecifica é discutida para essas doenças neurológicas crônicas.

Palavras-chave:HTLV-I, HAM/TSP, líquido cefalorraquidiano, índice de anticorpos.

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Aknowledgements - We would like to thank Dr. C. Poser for the review of this manuscript.

Aceite: 18-agosto-1995.

Dr. Marzia Puccioni Sohler - R Dezenove de Fevereiro 185/705 - 22280-030 Rio de Janeiro RJ - Brasil. FAX 55 21 5211175.

1. Ceroni M, Piccardo P, Rodgers-Johnson P, Mora C, Asher DM, Gajdusek DC, Gibbs CJ. Intrathecal synthesis of IgG antibodies to HTLV-I supports an etiological role for HTLV-I in tropical spastic paraparesis. Ann Neurol 1980, 23(Suppl):188-191.
2. Felgenhauer K, Reiber H. The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system. Clin Investig 1992, 70:28-37.
3. Felgenhauer K, Schädlich H -J, Nekic M, Ackermann R. Cerebrospinal fluid virus antibodies: a diagnostic indicator for multiple sclerosis? J Neurol Sci 1985, 71:291-299.
4. Gessain A, Caudie C, Gout O, Vernant J-C, Maurs L, Giordano C, Malone G, Tournier-Lasserve E, Essex M, de-The G. Intrathecal synthesis of antibodies to human T lymphotropic virus type I and the presence of IgG oligoclonal bands in the cerebrospinal fluid of patients with endemic tropical spastic paraparesis. J Infect Dis 1988, 167:1226-1234.
5. Godec MS, Asher DM, Murray RS, Shin ML, Greenham LW, Gibbs CJ, Gajdusek DC. Absence of measles, mumps, and rubella viral genomic sequences from multiple sclerosis brain tissue by polymerase chain reaction. Ann Neurol 1992, 32:401-404.
6. Graef IT, Henze T, Reiber H. Polyspezifische Immunreaktion im ZNS bei Autoimmunerkrankungen mit ZNS-Beteiligung. Zarztl. Fortbild 1994, 88:113-117.
7. Horikawa Y, Tsubaki T, Nakajima M. Rubella antibody in multiple sclerosis. Lancet 1973, 1:996-997.
8. Itoyama Y, Minato S-I, Kira J-I, Goto I, Okochi K, Yamamoto N. Immunological aspects of HTLV-I-associated myelopathy (HAM). In Roman G, Vernant J-C, Osame M (eds). HTLV-I and the nervous system. New York Alan R. Liss, p 287-295, 1992.
9. Jacobson S, Gupta A, Mattson D, Mingioli E, McFarlin DE. Immunological studies in tropical spastic paraparesis. Ann Neurol 1989, 27:149-166.
10. Kinnunen E, Valle M, Piirainen L, Kleemola M, Kantanen M -L, Juntunen J, Klockars M, Koskenvuo M. Viral antibodies in multiple sclerosis: a nationwide co-twin study. Arch Neurol 1990, 47:743-746.
11. Kira J-I, Itoyama Y, Koyanagi Y, Tateishi J, Kishikawa M, Akizuki S-I, Kobayashi I, Toki N, Sueishi K, Sato H, Sakaki Y, Yamamoto N, Goto I. Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy. Ann Neurol 1992, 31:39-45.
12. Kitze B, Turner RW, Burchhardt M, Poser S, Hunsmann G, Weber T. Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients. Clin Investig 1992, 70:1013-1018.
13. Lüer W, Poser S, Weber T, Jürgens S, Eichenlaub D, Pohle HD, Felgenhauer K. Chronic HIV encepalitis: I. Cerebrospinal fluid diagnosis. Klin Wochenschr 1988, 66:21-25.
14. Puccioni-Sohler M, Kitze B, Felgenhauer K. HTLV-I associated myelopathy (HAM/TSP) in patients from Brazil and Iran: neurological manifestations and CSF findings. Arq Neuropsiquiatr 1995, 52: 213-217.
15. Puccioni-Sohler M, Rieckmann P, Kitze B, Lange P, Abrecht M, Felgenhauer K. A soluble form of tumor necrosis factor receptor in cerebrospinal fluid and serum of HTLV-I-associated myelopathy and other neurological diseases. J Neurol 1995, 242: 239- 242.
16. Reiber H. Flow rate of cerebrospinal fluid (CSF): a concept common to normal blood-CSF barrier function and to dysfunction in neurological disease. J Neurol Sci 1994, 122: 189-203.
17. Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem 1991, 37:1163-1160.
18. Schädlich H-J, Mohrmann G, Nekic M, Felgenhauer K. Intrathecal synthesis of virus antibodies: a diagnostic test for multiple sclerosis. Eur Neurol 1990, 30:302-304.
19. Varela FJ, Coutinho A. Second generation immune networks. Immunol Today 1991, 12:166-169.

Publication Dates

Publication in this collection
08 Dec 2010
Date of issue
Dec 1995

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

[1] 1. Ceroni M, Piccardo P, Rodgers-Johnson P, Mora C, Asher DM, Gajdusek DC, Gibbs CJ. Intrathecal synthesis of IgG antibodies to HTLV-I supports an etiological role for HTLV-I in tropical spastic paraparesis. Ann Neurol 1980, 23(Suppl):188-191.

[2] 2. Felgenhauer K, Reiber H. The diagnostic significance of antibody specificity indices in multiple sclerosis and herpes virus induced diseases of the nervous system. Clin Investig 1992, 70:28-37.

[3] 3. Felgenhauer K, Schädlich H -J, Nekic M, Ackermann R. Cerebrospinal fluid virus antibodies: a diagnostic indicator for multiple sclerosis? J Neurol Sci 1985, 71:291-299.

[4] 4. Gessain A, Caudie C, Gout O, Vernant J-C, Maurs L, Giordano C, Malone G, Tournier-Lasserve E, Essex M, de-The G. Intrathecal synthesis of antibodies to human T lymphotropic virus type I and the presence of IgG oligoclonal bands in the cerebrospinal fluid of patients with endemic tropical spastic paraparesis. J Infect Dis 1988, 167:1226-1234.

[5] 5. Godec MS, Asher DM, Murray RS, Shin ML, Greenham LW, Gibbs CJ, Gajdusek DC. Absence of measles, mumps, and rubella viral genomic sequences from multiple sclerosis brain tissue by polymerase chain reaction. Ann Neurol 1992, 32:401-404.

[6] 6. Graef IT, Henze T, Reiber H. Polyspezifische Immunreaktion im ZNS bei Autoimmunerkrankungen mit ZNS-Beteiligung. Zarztl. Fortbild 1994, 88:113-117.

[7] 7. Horikawa Y, Tsubaki T, Nakajima M. Rubella antibody in multiple sclerosis. Lancet 1973, 1:996-997.

[8] 8. Itoyama Y, Minato S-I, Kira J-I, Goto I, Okochi K, Yamamoto N. Immunological aspects of HTLV-I-associated myelopathy (HAM). In Roman G, Vernant J-C, Osame M (eds). HTLV-I and the nervous system. New York Alan R. Liss, p 287-295, 1992.

[9] 9. Jacobson S, Gupta A, Mattson D, Mingioli E, McFarlin DE. Immunological studies in tropical spastic paraparesis. Ann Neurol 1989, 27:149-166.

[10] 10. Kinnunen E, Valle M, Piirainen L, Kleemola M, Kantanen M -L, Juntunen J, Klockars M, Koskenvuo M. Viral antibodies in multiple sclerosis: a nationwide co-twin study. Arch Neurol 1990, 47:743-746.

[11] 11. Kira J-I, Itoyama Y, Koyanagi Y, Tateishi J, Kishikawa M, Akizuki S-I, Kobayashi I, Toki N, Sueishi K, Sato H, Sakaki Y, Yamamoto N, Goto I. Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy. Ann Neurol 1992, 31:39-45.

[12] 12. Kitze B, Turner RW, Burchhardt M, Poser S, Hunsmann G, Weber T. Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients. Clin Investig 1992, 70:1013-1018.

[13] 13. Lüer W, Poser S, Weber T, Jürgens S, Eichenlaub D, Pohle HD, Felgenhauer K. Chronic HIV encepalitis: I. Cerebrospinal fluid diagnosis. Klin Wochenschr 1988, 66:21-25.

[14] 14. Puccioni-Sohler M, Kitze B, Felgenhauer K. HTLV-I associated myelopathy (HAM/TSP) in patients from Brazil and Iran: neurological manifestations and CSF findings. Arq Neuropsiquiatr 1995, 52: 213-217.

[15] 15. Puccioni-Sohler M, Rieckmann P, Kitze B, Lange P, Abrecht M, Felgenhauer K. A soluble form of tumor necrosis factor receptor in cerebrospinal fluid and serum of HTLV-I-associated myelopathy and other neurological diseases. J Neurol 1995, 242: 239- 242.

[16] 16. Reiber H. Flow rate of cerebrospinal fluid (CSF): a concept common to normal blood-CSF barrier function and to dysfunction in neurological disease. J Neurol Sci 1994, 122: 189-203.

[17] 17. Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem 1991, 37:1163-1160.

[18] 18. Schädlich H-J, Mohrmann G, Nekic M, Felgenhauer K. Intrathecal synthesis of virus antibodies: a diagnostic test for multiple sclerosis. Eur Neurol 1990, 30:302-304.

[19] 19. Varela FJ, Coutinho A. Second generation immune networks. Immunol Today 1991, 12:166-169.