Gradiente ventrículo-lombar de concentração das proteínas totais do líquido cefalorraquiano: 1 - Mecanismo de origem

Braga, Fernando Menezes; Reis-Filho, João Baptista dos; Camargo-Lima, José Geraldo de

doi:10.1590/S0004-282X1983000300006

Resumos

Foi feito estudo do mecanismo de origem do gradiente ventriculo-lombar de concentração das proteínas totais do LCR baseado no comportamento da taxa das proteínas totais e do título da reação de fixação de complemento para cisticerco em pacientes com neurocisticercose em atividade. O aumento concomitante da taxa das proteínas totais e da intensidade da reação imunitária, em amostras simultâneas cisternal e lombar do LCR de pacientes com comunicação livre no espaço subaracnóideo espinhal, e as grandes elevações simultâneas destes dados da semiologia no LCR lombar de pacientes que apresentaram bloqueio do espaço subaracnóideo espinhal, indicam que o gradiente de concentração das proteínas ao longo do neuro-eixo resulta da saída seletiva de água.

In normal conditions there is a concentration gradient of proteins along the neuraxis. From a low level in the ventricles, ranging from 5 to 15 mg/100 ml, to an intermediate level in the cisterna magna, the protein content reaches its highest level in the lumbar sac, 12 to 44 mg/100 ml. Several mechanisms were considered to elucidate the origin of this gradient but many investigators think that the progressive increase of the protein concentration is best explained by the transfer of proteins from serum to the cerebrospinal fluid due to the relatively raised permeability of blood-cerebrospinal fluid barrier in the spinal subarachnoid space. This paper presents a study of the protein concentrations in cisternal and lumbar cerebrospinal fluid samples of patients with neurocysticercosis in activity. The 11 patients of the first group had free subarachnoid space communication between the cisterna magna and the lumbar sac; the 6 patients of the second group had a complete block of the subarachnoid space between these two levels. In every cerebrospinal fluid specimen the quantitative complement fixation test for cysticercus was performed and the titer determined in order to make an assessment of the central nervous system humoral immune response. The analysis of the data of this investigation shows that the concentration gradient of proteins is evident in the cerebrospinal fluid of patients with patency of the spinal subarachnoid space, and the ratio of concentrations of protein contents in simultaneous cisternal and lumbar samples was similar to that one observed in normal individuals. This gradient is also detected when the intensity of the humoral immune response is determined by quantitative complement fixation test for cysticercus in simultaneous cisternal and lumbar specimens. After the onset of spinal subarachnoid block, the confront of the results of the tests in cerebrospinal fluid samples, obtained before and after the blockage, shows a large increase both in the total protein content as well as the intensity of the humoral immune response, in the lumbar level. The similar increases both in protein concentration and titer of cysticercus complement fixation test in the lumbar fluid, in comparison with the cisternal fluid, in patients with patent spinal subarachnoid space, and the large simultaneous and similar increases in both protein content and titer of the cysticercus complement fixation test in the lumbar fluid of patients with spinal subarachnoid block are in disagreement with the usual explanation of the origin mechanims of the gradient. If the large increase in the protein content were the consequence of its transfer from serum to cerebrospinal fluid, it would have determined a decrease in the intensity of the immune response because of the negative or low complement fixation test titer usually verified in blood serum. Due to the poor systemic repercussion of the humoral immune response, the blood serum has a low reagin concentration or no reagin at all. Thus, it would have resulted in a decrease of the reagin concentration, instead of the constant increase observed in the spinal fluid of the great majority of the patients of the two groups. The comparative study of the protein contents and of the degrees of the intensity of the immune response in the cerebrospinal fluid of patients with neurocysticercosis, with patency of the cistern-lumbar subarachnoid space, and with spinal subarachnoid space block, suggests that the cerebrospinal fluid protein concentration gradient is the consequence of the scape of water from the fluid.

Gradiente ventrículo-lombar de concentração das proteínas totais do líquido cefalorraquiano: 1 - Mecanismo de origem

Cerebrospinal fluid protein concentration gradient: 1. Mechanism of origin

Fernando Menezes Braga^I; João Baptista dos Reis-Filho^I; José Geraldo de Camargo-Lima^II

^IProfessor Adjunto. Escola Paulista de Medicina, Departamento de Neurologia e Neurocirurgia, Disciplina de Neurologia

^IIProfessor Titular. Escola Paulista de Medicina, Departamento de Neurologia e Neurocirurgia, Disciplina de Neurologia

RESUMO

Foi feito estudo do mecanismo de origem do gradiente ventriculo-lombar de concentração das proteínas totais do LCR baseado no comportamento da taxa das proteínas totais e do título da reação de fixação de complemento para cisticerco em pacientes com neurocisticercose em atividade. O aumento concomitante da taxa das proteínas totais e da intensidade da reação imunitária, em amostras simultâneas cisternal e lombar do LCR de pacientes com comunicação livre no espaço subaracnóideo espinhal, e as grandes elevações simultâneas destes dados da semiologia no LCR lombar de pacientes que apresentaram bloqueio do espaço subaracnóideo espinhal, indicam que o gradiente de concentração das proteínas ao longo do neuro-eixo resulta da saída seletiva de água.

SUMMARY

In normal conditions there is a concentration gradient of proteins along the neuraxis. From a low level in the ventricles, ranging from 5 to 15 mg/100 ml, to an intermediate level in the cisterna magna, the protein content reaches its highest level in the lumbar sac, 12 to 44 mg/100 ml. Several mechanisms were considered to elucidate the origin of this gradient but many investigators think that the progressive increase of the protein concentration is best explained by the transfer of proteins from serum to the cerebrospinal fluid due to the relatively raised permeability of blood-cerebrospinal fluid barrier in the spinal subarachnoid space. This paper presents a study of the protein concentrations in cisternal and lumbar cerebrospinal fluid samples of patients with neurocysticercosis in activity. The 11 patients of the first group had free subarachnoid space communication between the cisterna magna and the lumbar sac; the 6 patients of the second group had a complete block of the subarachnoid space between these two levels. In every cerebrospinal fluid specimen the quantitative complement fixation test for cysticercus was performed and the titer determined in order to make an assessment of the central nervous system humoral immune response. The analysis of the data of this investigation shows that the concentration gradient of proteins is evident in the cerebrospinal fluid of patients with patency of the spinal subarachnoid space, and the ratio of concentrations of protein contents in simultaneous cisternal and lumbar samples was similar to that one observed in normal individuals. This gradient is also detected when the intensity of the humoral immune response is determined by quantitative complement fixation test for cysticercus in simultaneous cisternal and lumbar specimens. After the onset of spinal subarachnoid block, the confront of the results of the tests in cerebrospinal fluid samples, obtained before and after the blockage, shows a large increase both in the total protein content as well as the intensity of the humoral immune response, in the lumbar level. The similar increases both in protein concentration and titer of cysticercus complement fixation test in the lumbar fluid, in comparison with the cisternal fluid, in patients with patent spinal subarachnoid space, and the large simultaneous and similar increases in both protein content and titer of the cysticercus complement fixation test in the lumbar fluid of patients with spinal subarachnoid block are in disagreement with the usual explanation of the origin mechanims of the gradient. If the large increase in the protein content were the consequence of its transfer from serum to cerebrospinal fluid, it would have determined a decrease in the intensity of the immune response because of the negative or low complement fixation test titer usually verified in blood serum. Due to the poor systemic repercussion of the humoral immune response, the blood serum has a low reagin concentration or no reagin at all. Thus, it would have resulted in a decrease of the reagin concentration, instead of the constant increase observed in the spinal fluid of the great majority of the patients of the two groups.

The comparative study of the protein contents and of the degrees of the intensity of the immune response in the cerebrospinal fluid of patients with neurocysticercosis, with patency of the cistern-lumbar subarachnoid space, and with spinal subarachnoid space block, suggests that the cerebrospinal fluid protein concentration gradient is the consequence of the scape of water from the fluid.

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Escola Paulista de Medicina, Departamento de Neurologia e Neurocirurgia, Disciplina de Neurologia - Rua Botucatu 740 - 04023 São Paulo, SP - Brasil.

1. BERING JR., E. A. - Choroid plexus and arterial pulsation of cerebrospinal fluid. Arch. Neurol. Psychiat. (Chicago) 73:165, 1955.
2. CUTLER, R. W. P.; MURRAY, J. E. CORNICK, L. R. - Variation in protein permeability in different regions of the cerebrospinal fluid. Exp. Neurol. 28:257, 1970.
3. DAVSON, H. - Physiology of the Cerebrospinal Fluid. Churchill, London, 1967.
4. DENIS, W. & AYER, J. B. - Method of quantitative determination of protein in cerebrospinal fluid. Arch. int. Med. 26:436, 1920.
5. DI CHIRO, G. - Observations on the circulation of the cerebrospinal fluid. Acta radiol. (Diag.) 5:988, 1966.
6. DI CHIRO, G.; HAMMOCK, M. K. & BLEYER, W. A. - Spinal descent of cerebrospinal fluid in man. Neurol. (Minneapolis) 26:1, 1976.
7. FISHMAN, R. R.; RANSOHOFF, J. & OSSERMAN, E. F. - Factors influencing the concentration gradient of protein in cerebrospinal fluid. J. clin. Invest. 37:1419, 1958.
8. GABBAI, A. A. - Contribuição ao estudo da reação de fixação de complemento para cisticerco no soro sanguíneo. Tese. Escola Paulista de Medicina, 1980.
9. HABECK, D. - Zur Verminderung des Gesamteiweissgehaltes in Liquor cerebrospinalis (unter besonderer Berücksichtigung der elektrophoretischen Vorfraktion). Arch. Psychiat. Z. ges. Neurologie 202:354, 1961.
10. HILL, N. C; McKENZIE, B. F.; McGUCKIN, W. F.; GOLDSTEIN, N. P. & SVIEN, H. J. - Proteins, glycoproteins and lipoproteins in the serum and spinal fluid of healthy subjects. Proc. Mayo Clin. 33:686, 1958.
11. HILL, N. C; GOLDSTEIN, N. P.; McKENZIE, B. F.; McGUCKIN, W. F. & SVIEN, H. J. - Cerebrospinal fluid proteins, glycoproteins, and lipoproteins in obstructive lesions of the nervous system. Brain 82:581, 1959.
12. HOCHWALD, G. M.; WALLENSTEIN, M. C. & MATHEWS, E. S. - Exchange of proteins between blood and spinal subarachnoid fluid. Am. J. Physiol. 217:348, 1969.
13. HOCHWALD, G. M. - Influx of serum proteins and their concentration in spinal fluid along the neuraxis. J. neurol. Sci. 10:269, 1980.
14. HOEPRICH, P. D. & WARD, J. R. - The Fluids of Parenteral Body Cavities. Grune & Stratton, New York, 1959.
15. LANGE, O. - Considerações sobre a eosinofilia do líquido cefaloraquidiano. Rev. Neurol. Psychiat. São Paulo 1:421, 1935.
16. LANGE, O. - O líquido cefalo-raquidiano na cisticercose encefálica. Rev. Neurol. Psychiat. São Paulo 2:52, 1936.
17. LIMA, A. T.; TANCREDI, F. & REIS, J. B. - O líquido cefalo-raquidiano cisternal o lombar. Conceito de normalidade. Arq. Assist. Psicopatas (São Paulo) 5:391, 1940.
18. LUPS, S. & HAAN, A. M. F. H. - The Cerebrospinal Fluid. Elsevier, Amsterdam, 1954.
19. LÜTHY, F. - Liquor cerebrospinalis. In Handbuch der Inneren Medizin. IV Auf. - V/1 - Neurologic Springer, Berlin, 1953.
20. MADONICK, M. J. & WEISSMAN, F. - The total spinal fluid protein concentration in patients over 65. Geriatrics 10:533, 1955.
21. MERRITT, H. H. & FREMONT-SMITH, F. - The Cerebrospinal Fluid. Saunders, Philadelphia. 1938.
22. MOLLARET, M. P. - Technique de prélèvement et caractères normaux du liquide céphalo-rachidien lombaire et sous-occipitale de quelques espécies de singes. Comptes. rend. Soe. Biol. 117:1095, 1934.
23. MOSES, A. - Dos metodos biolojicos de diagnostico nas cisticercozes. Mem. Inst. Oswaldo Cruz (Rio de Janeiro) 3:320, 1911.
24. OLDENDORF, W. H. & DAVSON, H. - Brain extracellular space and the sink action of cerebrospinal fluid. Arch. Neurol. (Chicago) 17:196, 1967.
25. PUPO, P. P.; CARDOSO, W.; REIS, J. B. & SILVA, C. P. - Sobre a cisticercose encefálica: estudo clínico, anatomopatológico, radiológico e do líquido cefalorraquidiano. Arq. Assist. Psieopatas (São Paulo) 10-11:3, 1945, 1946.
26. REIS, J. B. - Determinação da taxa das proteínas totais, albumina e globulinas do líquido céfalo-raquidiano com o nefelometro de Pulfrich. Arq. Assist. Psicopatas (São Paulo) 3:5, 1938.
27. REIS, J. B. & BEI, A. - A reação de fixação de complemento para o diagnóstico da sífilis e da cisticercose no líquido cefalorraqueano pela técnica de Wadsworth, Maltaner & Maltaner. Rev. paul. Med. 53:439, 1958.
28. REIS, J. B.; BEI, A.; REIS-FILHO, J. B. & NASSER, J. - Líquido cefalorraquiano na cisticercose encefálica. Arq. Neuro-Psiquiat. (São Paulo) 37:113, 1979.
29. REIS, J. B.; BEI, A. & REIS-FILHO, J. B. - Líquido Cefalorraquiano. Sarvier, São Paulo, 1980.
30. SCHMIDT, C. & MATIAR, H. - Das quantitative Verhältnis der Serum und Liquorproteine. Dtsch. Z. Nervenh. 174:443, 1956.
31. SPINA-FRANÇA, A. - Cisticercose do sistema nervoso central. Considerações sobre 50 casos. Rev. paul. Med. 48:58, 1956.
32. SPINA-FRANÇA, A. - Valor do exame eletroforético das proteínas do líquido cefalorraquidiano na cisticercose do sistema nervoso central. Tese. Faculdade de Medicina da U.S.P., 1960.
33. SWEET, W. H. et al. - The formation, flow and absorption of cerebrospinal fluid; newer concepts based on studies with isotopes. Citado por Bowsher, D., Cerebrospinal Fluid Dynamics in Health and Disease. Thomas, Springfield, 1960.
34. TVETEN, L. - Cerebrospinal fluid proteins in obstructive lesions of the central nervous system. Acta, neurol. Scand. 41:80, 1965.
35. WEISNER, B. & BERNHARDT, W. - Protein fractions of lumbar, cisternal and ventricular fluids. J. neurol. Sci. 37:205, 1978.

Datas de Publicação

Publicação nesta coleção
14 Ago 2012
Data do Fascículo
Set 1983

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

[1] 1. BERING JR., E. A. - Choroid plexus and arterial pulsation of cerebrospinal fluid. Arch. Neurol. Psychiat. (Chicago) 73:165, 1955.

[2] 2. CUTLER, R. W. P.; MURRAY, J. E. CORNICK, L. R. - Variation in protein permeability in different regions of the cerebrospinal fluid. Exp. Neurol. 28:257, 1970.

[3] 3. DAVSON, H. - Physiology of the Cerebrospinal Fluid. Churchill, London, 1967.

[4] 4. DENIS, W. & AYER, J. B. - Method of quantitative determination of protein in cerebrospinal fluid. Arch. int. Med. 26:436, 1920.

[5] 5. DI CHIRO, G. - Observations on the circulation of the cerebrospinal fluid. Acta radiol. (Diag.) 5:988, 1966.

[6] 6. DI CHIRO, G.; HAMMOCK, M. K. & BLEYER, W. A. - Spinal descent of cerebrospinal fluid in man. Neurol. (Minneapolis) 26:1, 1976.

[7] 7. FISHMAN, R. R.; RANSOHOFF, J. & OSSERMAN, E. F. - Factors influencing the concentration gradient of protein in cerebrospinal fluid. J. clin. Invest. 37:1419, 1958.

[8] 8. GABBAI, A. A. - Contribuição ao estudo da reação de fixação de complemento para cisticerco no soro sanguíneo. Tese. Escola Paulista de Medicina, 1980.

[9] 9. HABECK, D. - Zur Verminderung des Gesamteiweissgehaltes in Liquor cerebrospinalis (unter besonderer Berücksichtigung der elektrophoretischen Vorfraktion). Arch. Psychiat. Z. ges. Neurologie 202:354, 1961.

[10] 10. HILL, N. C; McKENZIE, B. F.; McGUCKIN, W. F.; GOLDSTEIN, N. P. & SVIEN, H. J. - Proteins, glycoproteins and lipoproteins in the serum and spinal fluid of healthy subjects. Proc. Mayo Clin. 33:686, 1958.

[11] 11. HILL, N. C; GOLDSTEIN, N. P.; McKENZIE, B. F.; McGUCKIN, W. F. & SVIEN, H. J. - Cerebrospinal fluid proteins, glycoproteins, and lipoproteins in obstructive lesions of the nervous system. Brain 82:581, 1959.

[12] 12. HOCHWALD, G. M.; WALLENSTEIN, M. C. & MATHEWS, E. S. - Exchange of proteins between blood and spinal subarachnoid fluid. Am. J. Physiol. 217:348, 1969.

[13] 13. HOCHWALD, G. M. - Influx of serum proteins and their concentration in spinal fluid along the neuraxis. J. neurol. Sci. 10:269, 1980.

[14] 14. HOEPRICH, P. D. & WARD, J. R. - The Fluids of Parenteral Body Cavities. Grune & Stratton, New York, 1959.

[15] 15. LANGE, O. - Considerações sobre a eosinofilia do líquido cefaloraquidiano. Rev. Neurol. Psychiat. São Paulo 1:421, 1935.

[16] 16. LANGE, O. - O líquido cefalo-raquidiano na cisticercose encefálica. Rev. Neurol. Psychiat. São Paulo 2:52, 1936.

[17] 17. LIMA, A. T.; TANCREDI, F. & REIS, J. B. - O líquido cefalo-raquidiano cisternal o lombar. Conceito de normalidade. Arq. Assist. Psicopatas (São Paulo) 5:391, 1940.

[18] 18. LUPS, S. & HAAN, A. M. F. H. - The Cerebrospinal Fluid. Elsevier, Amsterdam, 1954.

[19] 19. LÜTHY, F. - Liquor cerebrospinalis. In Handbuch der Inneren Medizin. IV Auf. - V/1 - Neurologic Springer, Berlin, 1953.

[20] 20. MADONICK, M. J. & WEISSMAN, F. - The total spinal fluid protein concentration in patients over 65. Geriatrics 10:533, 1955.

[21] 21. MERRITT, H. H. & FREMONT-SMITH, F. - The Cerebrospinal Fluid. Saunders, Philadelphia. 1938.

[22] 22. MOLLARET, M. P. - Technique de prélèvement et caractères normaux du liquide céphalo-rachidien lombaire et sous-occipitale de quelques espécies de singes. Comptes. rend. Soe. Biol. 117:1095, 1934.

[23] 23. MOSES, A. - Dos metodos biolojicos de diagnostico nas cisticercozes. Mem. Inst. Oswaldo Cruz (Rio de Janeiro) 3:320, 1911.

[24] 24. OLDENDORF, W. H. & DAVSON, H. - Brain extracellular space and the sink action of cerebrospinal fluid. Arch. Neurol. (Chicago) 17:196, 1967.

[25] 25. PUPO, P. P.; CARDOSO, W.; REIS, J. B. & SILVA, C. P. - Sobre a cisticercose encefálica: estudo clínico, anatomopatológico, radiológico e do líquido cefalorraquidiano. Arq. Assist. Psieopatas (São Paulo) 10-11:3, 1945, 1946.

[26] 26. REIS, J. B. - Determinação da taxa das proteínas totais, albumina e globulinas do líquido céfalo-raquidiano com o nefelometro de Pulfrich. Arq. Assist. Psicopatas (São Paulo) 3:5, 1938.

[27] 27. REIS, J. B. & BEI, A. - A reação de fixação de complemento para o diagnóstico da sífilis e da cisticercose no líquido cefalorraqueano pela técnica de Wadsworth, Maltaner & Maltaner. Rev. paul. Med. 53:439, 1958.

[28] 28. REIS, J. B.; BEI, A.; REIS-FILHO, J. B. & NASSER, J. - Líquido cefalorraquiano na cisticercose encefálica. Arq. Neuro-Psiquiat. (São Paulo) 37:113, 1979.

[29] 29. REIS, J. B.; BEI, A. & REIS-FILHO, J. B. - Líquido Cefalorraquiano. Sarvier, São Paulo, 1980.

[30] 30. SCHMIDT, C. & MATIAR, H. - Das quantitative Verhältnis der Serum und Liquorproteine. Dtsch. Z. Nervenh. 174:443, 1956.

[31] 31. SPINA-FRANÇA, A. - Cisticercose do sistema nervoso central. Considerações sobre 50 casos. Rev. paul. Med. 48:58, 1956.

[32] 32. SPINA-FRANÇA, A. - Valor do exame eletroforético das proteínas do líquido cefalorraquidiano na cisticercose do sistema nervoso central. Tese. Faculdade de Medicina da U.S.P., 1960.

[33] 33. SWEET, W. H. et al. - The formation, flow and absorption of cerebrospinal fluid; newer concepts based on studies with isotopes. Citado por Bowsher, D., Cerebrospinal Fluid Dynamics in Health and Disease. Thomas, Springfield, 1960.

[34] 34. TVETEN, L. - Cerebrospinal fluid proteins in obstructive lesions of the central nervous system. Acta, neurol. Scand. 41:80, 1965.

[35] 35. WEISNER, B. & BERNHARDT, W. - Protein fractions of lumbar, cisternal and ventricular fluids. J. neurol. Sci. 37:205, 1978.