Efeitos de derivados benzodiazepines na epilepsia: estudos eletrencefalográficos longitudinais

Lison, Michel Pierre

doi:10.1590/S0004-282X1970000300004

Resumos

Foram estudadas as modificações do quadro eletrencefalográfico em 24 crianças com manifestações epilépticas diárias, tratadas com derivados da benzodiazepina. O conjunto dos fenômenos eletrencefalográficos observados durante os seguimentos terapêuticos longitudinais traduz uma modificação importante dos mecanismos subcorticais envolvidos na gênese das crises convulsivas e na produção das descargas paroxísticas. Os fatos observados coadunam-se com a teoria de uma ação benzodiazepínica sobre o sistema reticular talâmico inespecífico. A ação benzodiazepínica predomina sobre o sistema de inibição ativo anexo ao sistema de projeção talamocortical. Discute-se ainda se essa ação se faz diretamente, através de formações quimiosensíveis existentes no seio do sistema reticular talâmico e/ou indiretamente, pela depressão de certas estruturas do sistema límbico, modificando desta forma o "feed-back" de importantes circuitos subcorticais que podem influenciar os neurônios centrencefálicos hiperexcitáveis.

The modifications of the electroencephalic patterns in 24 childrens with daily epileptic seizures treated by benzodiazepine derivatives were studied. The electroencephalographic findings during the longitudinal therapeutic follow-ups disclose important modifications of the subcortical mechanisms involved in the production of the convulsive seizures and paroxistical discharges. These facts are in accordance with the hypothesis that benzodiazepine derivatives act upon the non-specific thalamic reticular system. The benzodiazepine derivatives are more active upon the inhibitory system related to the thalamocortical projection system. Two hypothesis are discussed: 1 — the drugs act upon chemoreceptors present in the thalamic reticular system; 2 — the act indirectly, depressing some elements of the limbic system and modifying in this way the feed-back of subcortical circuits which discharge upon hyperactive centrencephalic neurons.

Efeitos de derivados benzodiazepines na epilepsia. estudos eletrencefalográficos longitudinais

The effects of benzodiazepine dérivâtes in epilepsies. Longitudinal electroencephalographic studies

Michel Pierre Lison

Departamento de Neuropsiquiatria e Psicologia Médica Faculdade de Medicina Ribeirão Prêto, SP Brasil

RESUMO

Foram estudadas as modificações do quadro eletrencefalográfico em 24 crianças com manifestações epilépticas diárias, tratadas com derivados da benzodiazepina.

O conjunto dos fenômenos eletrencefalográficos observados durante os seguimentos terapêuticos longitudinais traduz uma modificação importante dos mecanismos subcorticais envolvidos na gênese das crises convulsivas e na produção das descargas paroxísticas. Os fatos observados coadunam-se com a teoria de uma ação benzodiazepínica sobre o sistema reticular talâmico inespecífico. A ação benzodiazepínica predomina sobre o sistema de inibição ativo anexo ao sistema de projeção talamocortical. Discute-se ainda se essa ação se faz diretamente, através de formações quimiosensíveis existentes no seio do sistema reticular talâmico e/ou indiretamente, pela depressão de certas estruturas do sistema límbico, modificando desta forma o "feed-back" de importantes circuitos subcorticais que podem influenciar os neurônios centrencefálicos hiperexcitáveis.

SUMMARY

The modifications of the electroencephalic patterns in 24 childrens with daily epileptic seizures treated by benzodiazepine derivatives were studied.

The electroencephalographic findings during the longitudinal therapeutic follow-ups disclose important modifications of the subcortical mechanisms involved in the production of the convulsive seizures and paroxistical discharges. These facts are in accordance with the hypothesis that benzodiazepine derivatives act upon the non-specific thalamic reticular system. The benzodiazepine derivatives are more active upon the inhibitory system related to the thalamocortical projection system. Two hypothesis are discussed: 1 the drugs act upon chemoreceptors present in the thalamic reticular system; 2 the act indirectly, depressing some elements of the limbic system and modifying in this way the feed-back of subcortical circuits which discharge upon hyperactive centrencephalic neurons.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Departamento de Neuropsiquiatria e Psicologia Médica Faculdade de Medicina Ribeirão Prêto, SP Brasil.

Nota do autor Este trabalho constitui parte da tese apresentada para concurso à Docência Livre da Clínica Neurológica na Faculdade de Medicina de Ribeirão Preto. Universidade de São Paulo.

1. BANCAUD, J.; TALAIRACH, J.; MOREL, P. & BRESSON, M. La corne d'Ammon et le noyau amygdalien: effects cliniques et électriques de leur stimulation chez l'homme. Rev. Neurol. (Paris) 115:329, 1966.
2. BRAZIER, M. A. B. The effects of drugs on the electroencephalogran in man. Clin. Pharmacol. Ther. 5:102, 1964.
3. BRODIE, R. E. e DOW, R. S. Chordiazepoxide in epilepsy. Northwest Med. 61:513, 1962.
4. CADILHAC, J. & PASSOUANT, P. Influence of various phases of night sleep on the epileptic discharges in man. Electroencephal. Clin. Neurophysiol. 17: 441, 1964.
5. CASO, A. & FERNANDEZ, G. R. Estudio neuropsiquiátrico de enfermos epilépticos tratados com diversos derivados de la benzodiazepina. Neurol. Neurocir. Psiquiat. (México) 3:184, 1962.
6. DELANGE, M.; CASTAN, P.; CADILHAC, J. & PASSOUANT, P. Étude du sommeil de nuit au cours d'épilepsies centrencéphaliques et temporales. Rev. Neurol. (Paris) 106:106, 1962.
7. EIDELBERG, E.; NEER, H. M. & MILLER, M. K. Anticonvulsant properties of some benzodiazepine derivaties. Possible use against psychomotor seizures. Neurology 15:223, 1965.
8. GASTAUT, H.; NAQUET, R.; VIGOUROUX, R.; ROGER, A. & BADIER, M. Étude electrographique chez l'homme et chez l'animal des décharges épileptiques dites psychomotrices. Rev. Neurol. (Paris) 88:310, 1953.
9. GASTAUT, H. & FISCHER-WILLIAMS, M. The physiopathology of epileptic seizures. In Handbook of Physiology Neurophysiology I, Ed. por J. Field, H. W. Magoun e V. E. Hall. American Physiological Society, Washington, 1959 pags. 329-363.
10. GASTAUT, H.; RÉGIS, H. & CHEVALLIER A propos du Petit Mal "akinétique" de Lennox. Rev. Neurol. (Paris) 103:593, 1960.
11. GASTAUT, H.; ROGER, J.; TIMSIT, M. & BROUGHTON, R. An electroclinical study of generalized epileptic seizure of tonic expression. Epilepsia Amsterdam) 4:15, 1963.
12. GASTAUT, H.; BATINI, C; FRESSY, J.; BROUGHTON, R. & TASSINARI, C. A. Étude électrographique du sommeil nocturne chez les épileptiques. Rev. Neurol. (Paris) 110:311, 1964.
13. GASTAUT, H.; CAVENESS, W. F.; LANDOLT, H.; LORENTZ DE HASS, A. M.; MC NAUGHTON, F. L.; MAGNUS, O.; MERLIS, J. R.; POND, D. A.; RADERMECKER, J. & STORM VAN LEEUWEN, W. A proposed international classification of epileptic seizures. Epilepsia (Amsterdam) 5:297, 1964.
14. GASTAUT, H. & PINSARD, N. The electroencephalogram in children suffering from cerebral seizures. In Second Advanced Course in Electroencephalography. Ed. por L. Koissier, Verlag der Wiener Medizinischen Akademie, Viena 1965, pag. 8195.
15. GASTAUT, H.; ROGER, J.; LOB, H. & TASSINARI, C. A. Les nouveaux médicaments anti-épileptiques. Encéphale 54:407, 1965.
16. GASTAUT, H.; ROGER, J.; LOB, H. & TASSINARI, C. A. L'action du Diazépan ("Valium") dans le traitement des formes non convulsives de l'épilepsie généralised (absences et états d'absences de types divers). Sem. Hôp. Paris 41: 1541, 1965.
17. GASTAUT, H.; ROGER, J.; SOULAYROL, R.; TASSINARI, C. A.; REGIS, H.; DRAVET C.; BERNARD, R.; PINSARD, N. & SAINT-JEAN, M. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as "Petit Mai Variant") or Lennox syndrome. Epilepsia (Amsterdam) 7:139, 1966.
18. GIBBS, E. L. & GIBBS, F. A. Extreme spindles: correlation of electroencephalographic sleep pattern with mental retardation. Science 138:1106, 1962.
19. GIBBS, F. A. & ANDERSON, E. M. Treatment of hypsarhythmia and infantile spasms with a Librium analogue. Neurology (Minneapolis) 15:1173, 1965.
20. GLASER, G. H. & COLUB, L. M. The electroencephalogram of psychomotor seizures in childhood. Electroencephal. Clin. Neurophysiol. 7:329, 1955.
21. HENRIKSEN, P. B. Acute treatment of epileptic seizures with diazepamum (Valium). In Proceedings of the eighteenth Congress of Scandinavian Neurologists, Helsinki, 1967. Edited by Hokkanen, E. Acta Neurol. Scand Suppl. 31, pag. 168, 1967.
22. HERNANDEZ PEÓN, R.; RINCON, J. T. & CHÁVEZ, G. I. Estudio clinico, electromiográfico y electroencefalográfico sobre las acciones relajante y anticonvulsiva del Ro 5-2807. Neurol. Neurocir. Psiquiat. (México) 3:174, 1962.
23. HERNÁNDEZ PEÓN, R.; ROJAS-RAMIREZ, J. A.; O'FLAHERTY, J. J. & MAZZUCHELLI-O'FLAHERTY, A. L. An experimental study of the anticonvulsive and relaxant action of Valium. Int. J. Pharmacol. 3:405, 1964.
24. HIMWICH, HE.; MORILLO, A. & STEINER, W. G. Drugs affecting rhinencephalic structures. J. Neuropsychiat. (Chicago) Supl. ad 3:15, 1962.
25. JAFFE, R. & CHRISTOFF, N. J. Intravenous diazepam in seizure disorders. Electroencephal. Clin. Neurophysiol. 23:96, 1967.
26. JASPER, H. H. The ten twenty electrode system of the international federation. Electroencephal. Clin. Neurpphysiol. 10:371, 1958.
27. KAADA, B. R. Somato-motor, autonomic and electroencephalographic responses to electrical stimulation of rhinencephalic and other structures in primats, cat and dog. Acta. Physiol. Scand Supl. 83, 1957.
28. LANOIR, J.; REQUIN, S.; DOLCE, G. & QUIRINOS, E. Étude neurophysiologique comparative de deux drogues anticonvulsivantes: le Valium et le Mogadon. VI Internat. Congress Electroencephal. Clin. Neurophysiol., Viena, 5:10, 1965; pags. 49-51.
29. LEFČVRE, A. B. & GAZAL, S. Tratamento do estado de mal epiléptico em crianças pelo Valium. Arq. Neuro-Psiquiat. (Săo Paulo) 26:155, 196S.
30. LENNOX, M. A. & ROBINSON, F. Cingulate cerebellar mechanisms in the physiological pathogenesis of epilepsy. Electroencephal. Clin. Neurophysiol. 3: 197, 1951.
31. LENNOX, W. G. & LENNOX, M. A. Epilepsy and Related Disorders. Little & Brown, Boston, 1960.
32. LISKE, E. & FORSTER, F. M. Clinical study of a new benzodiazepine as an anticonvulsivant agent. J. New Drugs (New York) 3:241, 1963.
33. LOMBROSO, C. T. Treatment of status epilepticus with diazepam. Neurology 16:629, 1966.
34. MASCIOCCHI, A. Metaminodiazepoxide (Librium) in the treatment of epilepsy. (Clinical and electroencephalographic study). Electroencephal. Clin. Neurophysiol. 15:919, 1963.
35. MAZARS, Y.; MAZARS, G.; GOTUSSO, C. & MERIENNE, L. Place de l'epilepsie cingulaire dans le cadre des épilepsies focales corticales. Rev. Neurol. (Paris) 114:225, 1966.
36. MEGA, D. y LISON, M. P. Valium endovenoso no tratamento do estado de mal epiléptico. Arq. Neuro-Psiquiat. (Săo Paulo) 26:145, 1968.
37. MILLICHAP, J. G. & ORTIZ, W. R. Nitrazepam in myoclonic epilepsies. Am. J. Dis. Child. 112:242, 1966.
38. MIRIBEL, J.; FAVEL, P.; NIETO, M.; GÉRIN,, P. & COURJON, J. Situation nosologique des crises toniques axiales dans le cadre de l'épilepsie. A propos de 18 observations. Rev. Neurol. (Paris) 109:324, 1963.
39. MÜLLER, H. R.; KLINGLER, M.; KAESER, H. E.; WURMSER, P. & HIRT, H. R. Zur Behandlung des Status Epilepticus mit Diezepam (Valium). Erfahrungen in 12 Fällen. Sshweiz. Med. Wschr. 96:121, 1966.
40. NAQUET, R.; SOULAYROL, R.; DOLCE, G.; TASSINARI, C. A.; BROUGHTON, R. & LOEB, H. First attempt at treatment of experimental status epilepticus in animals and spontaneous status epilepticus in man with diazepam (Valium). Electroencephal. Clin. Neurophysiol. 18:427, 1964.
41. NIEDERMEYER, E. The occurrence of centrencephalic and focal seizure patterns in the same patient. Electroencephal. Clin. Neurophysiol. 23:87, 1967.
42. NIETO, D.; CASTRO, M.; CARBAJAL, L.; ESTRADA, J.; HURTADO, A.; PEREZ JIMENEZ, E. & MOLINA, F. Tratamiento de la epilepsia com nuevo derivado de la benzodiazepina (Valium Ro 5-2807). Neurol. Neurocir. Psiquiat. (México) 3:168, 1962.
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Datas de Publicação

Publicação nesta coleção
22 Abr 2013
Data do Fascículo
Set 1970

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

[1] 1. BANCAUD, J.; TALAIRACH, J.; MOREL, P. & BRESSON, M. La corne d'Ammon et le noyau amygdalien: effects cliniques et électriques de leur stimulation chez l'homme. Rev. Neurol. (Paris) 115:329, 1966.

[2] 2. BRAZIER, M. A. B. The effects of drugs on the electroencephalogran in man. Clin. Pharmacol. Ther. 5:102, 1964.

[3] 3. BRODIE, R. E. e DOW, R. S. Chordiazepoxide in epilepsy. Northwest Med. 61:513, 1962.

[4] 4. CADILHAC, J. & PASSOUANT, P. Influence of various phases of night sleep on the epileptic discharges in man. Electroencephal. Clin. Neurophysiol. 17: 441, 1964.

[5] 5. CASO, A. & FERNANDEZ, G. R. Estudio neuropsiquiátrico de enfermos epilépticos tratados com diversos derivados de la benzodiazepina. Neurol. Neurocir. Psiquiat. (México) 3:184, 1962.

[6] 6. DELANGE, M.; CASTAN, P.; CADILHAC, J. & PASSOUANT, P. Étude du sommeil de nuit au cours d'épilepsies centrencéphaliques et temporales. Rev. Neurol. (Paris) 106:106, 1962.

[7] 7. EIDELBERG, E.; NEER, H. M. & MILLER, M. K. Anticonvulsant properties of some benzodiazepine derivaties. Possible use against psychomotor seizures. Neurology 15:223, 1965.

[8] 8. GASTAUT, H.; NAQUET, R.; VIGOUROUX, R.; ROGER, A. & BADIER, M. Étude electrographique chez l'homme et chez l'animal des décharges épileptiques dites psychomotrices. Rev. Neurol. (Paris) 88:310, 1953.

[9] 9. GASTAUT, H. & FISCHER-WILLIAMS, M. The physiopathology of epileptic seizures. In Handbook of Physiology Neurophysiology I, Ed. por J. Field, H. W. Magoun e V. E. Hall. American Physiological Society, Washington, 1959 pags. 329-363.

[10] 10. GASTAUT, H.; RÉGIS, H. & CHEVALLIER A propos du Petit Mal "akinétique" de Lennox. Rev. Neurol. (Paris) 103:593, 1960.

[11] 11. GASTAUT, H.; ROGER, J.; TIMSIT, M. & BROUGHTON, R. An electroclinical study of generalized epileptic seizure of tonic expression. Epilepsia Amsterdam) 4:15, 1963.

[12] 12. GASTAUT, H.; BATINI, C; FRESSY, J.; BROUGHTON, R. & TASSINARI, C. A. Étude électrographique du sommeil nocturne chez les épileptiques. Rev. Neurol. (Paris) 110:311, 1964.

[13] 13. GASTAUT, H.; CAVENESS, W. F.; LANDOLT, H.; LORENTZ DE HASS, A. M.; MC NAUGHTON, F. L.; MAGNUS, O.; MERLIS, J. R.; POND, D. A.; RADERMECKER, J. & STORM VAN LEEUWEN, W. A proposed international classification of epileptic seizures. Epilepsia (Amsterdam) 5:297, 1964.

[14] 14. GASTAUT, H. & PINSARD, N. The electroencephalogram in children suffering from cerebral seizures. In Second Advanced Course in Electroencephalography. Ed. por L. Koissier, Verlag der Wiener Medizinischen Akademie, Viena 1965, pag. 8195.

[15] 15. GASTAUT, H.; ROGER, J.; LOB, H. & TASSINARI, C. A. Les nouveaux médicaments anti-épileptiques. Encéphale 54:407, 1965.

[16] 16. GASTAUT, H.; ROGER, J.; LOB, H. & TASSINARI, C. A. L'action du Diazépan ("Valium") dans le traitement des formes non convulsives de l'épilepsie généralised (absences et états d'absences de types divers). Sem. Hôp. Paris 41: 1541, 1965.

[17] 17. GASTAUT, H.; ROGER, J.; SOULAYROL, R.; TASSINARI, C. A.; REGIS, H.; DRAVET C.; BERNARD, R.; PINSARD, N. & SAINT-JEAN, M. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as "Petit Mai Variant") or Lennox syndrome. Epilepsia (Amsterdam) 7:139, 1966.

[18] 18. GIBBS, E. L. & GIBBS, F. A. Extreme spindles: correlation of electroencephalographic sleep pattern with mental retardation. Science 138:1106, 1962.

[19] 19. GIBBS, F. A. & ANDERSON, E. M. Treatment of hypsarhythmia and infantile spasms with a Librium analogue. Neurology (Minneapolis) 15:1173, 1965.

[20] 20. GLASER, G. H. & COLUB, L. M. The electroencephalogram of psychomotor seizures in childhood. Electroencephal. Clin. Neurophysiol. 7:329, 1955.

[21] 21. HENRIKSEN, P. B. Acute treatment of epileptic seizures with diazepamum (Valium). In Proceedings of the eighteenth Congress of Scandinavian Neurologists, Helsinki, 1967. Edited by Hokkanen, E. Acta Neurol. Scand Suppl. 31, pag. 168, 1967.

[22] 22. HERNANDEZ PEÓN, R.; RINCON, J. T. & CHÁVEZ, G. I. Estudio clinico, electromiográfico y electroencefalográfico sobre las acciones relajante y anticonvulsiva del Ro 5-2807. Neurol. Neurocir. Psiquiat. (México) 3:174, 1962.

[23] 23. HERNÁNDEZ PEÓN, R.; ROJAS-RAMIREZ, J. A.; O'FLAHERTY, J. J. & MAZZUCHELLI-O'FLAHERTY, A. L. An experimental study of the anticonvulsive and relaxant action of Valium. Int. J. Pharmacol. 3:405, 1964.

[24] 24. HIMWICH, HE.; MORILLO, A. & STEINER, W. G. Drugs affecting rhinencephalic structures. J. Neuropsychiat. (Chicago) Supl. ad 3:15, 1962.

[25] 25. JAFFE, R. & CHRISTOFF, N. J. Intravenous diazepam in seizure disorders. Electroencephal. Clin. Neurophysiol. 23:96, 1967.

[26] 26. JASPER, H. H. The ten twenty electrode system of the international federation. Electroencephal. Clin. Neurpphysiol. 10:371, 1958.

[27] 27. KAADA, B. R. Somato-motor, autonomic and electroencephalographic responses to electrical stimulation of rhinencephalic and other structures in primats, cat and dog. Acta. Physiol. Scand Supl. 83, 1957.

[28] 28. LANOIR, J.; REQUIN, S.; DOLCE, G. & QUIRINOS, E. Étude neurophysiologique comparative de deux drogues anticonvulsivantes: le Valium et le Mogadon. VI Internat. Congress Electroencephal. Clin. Neurophysiol., Viena, 5:10, 1965; pags. 49-51.

[29] 29. LEFČVRE, A. B. & GAZAL, S. Tratamento do estado de mal epiléptico em crianças pelo Valium. Arq. Neuro-Psiquiat. (Săo Paulo) 26:155, 196S.

[30] 30. LENNOX, M. A. & ROBINSON, F. Cingulate cerebellar mechanisms in the physiological pathogenesis of epilepsy. Electroencephal. Clin. Neurophysiol. 3: 197, 1951.

[31] 31. LENNOX, W. G. & LENNOX, M. A. Epilepsy and Related Disorders. Little & Brown, Boston, 1960.

[32] 32. LISKE, E. & FORSTER, F. M. Clinical study of a new benzodiazepine as an anticonvulsivant agent. J. New Drugs (New York) 3:241, 1963.

[33] 33. LOMBROSO, C. T. Treatment of status epilepticus with diazepam. Neurology 16:629, 1966.

[34] 34. MASCIOCCHI, A. Metaminodiazepoxide (Librium) in the treatment of epilepsy. (Clinical and electroencephalographic study). Electroencephal. Clin. Neurophysiol. 15:919, 1963.

[35] 35. MAZARS, Y.; MAZARS, G.; GOTUSSO, C. & MERIENNE, L. Place de l'epilepsie cingulaire dans le cadre des épilepsies focales corticales. Rev. Neurol. (Paris) 114:225, 1966.

[36] 36. MEGA, D. y LISON, M. P. Valium endovenoso no tratamento do estado de mal epiléptico. Arq. Neuro-Psiquiat. (Săo Paulo) 26:145, 1968.

[37] 37. MILLICHAP, J. G. & ORTIZ, W. R. Nitrazepam in myoclonic epilepsies. Am. J. Dis. Child. 112:242, 1966.

[38] 38. MIRIBEL, J.; FAVEL, P.; NIETO, M.; GÉRIN,, P. & COURJON, J. Situation nosologique des crises toniques axiales dans le cadre de l'épilepsie. A propos de 18 observations. Rev. Neurol. (Paris) 109:324, 1963.

[39] 39. MÜLLER, H. R.; KLINGLER, M.; KAESER, H. E.; WURMSER, P. & HIRT, H. R. Zur Behandlung des Status Epilepticus mit Diezepam (Valium). Erfahrungen in 12 Fällen. Sshweiz. Med. Wschr. 96:121, 1966.

[40] 40. NAQUET, R.; SOULAYROL, R.; DOLCE, G.; TASSINARI, C. A.; BROUGHTON, R. & LOEB, H. First attempt at treatment of experimental status epilepticus in animals and spontaneous status epilepticus in man with diazepam (Valium). Electroencephal. Clin. Neurophysiol. 18:427, 1964.

[41] 41. NIEDERMEYER, E. The occurrence of centrencephalic and focal seizure patterns in the same patient. Electroencephal. Clin. Neurophysiol. 23:87, 1967.

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[43] 43. OLLER-DAURELLA, L. El Vadium e el Mogadon en el tratamiento de los automatismos. Rev. Esp. Oto-neuro-oftalm y Neurocir. 24:233, 1965.

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Brasil

Efeitos de derivados benzodiazepines na epilepsia: estudos eletrencefalográficos longitudinais

The effects of benzodiazepine dérivâtes in epilepsies: longitudinal electroencephalographic studies

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