Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls

Bigarella, Mônica M.; Mäder, Maria J.; Doro, Maribel P.; Gorz, Ana M.; Marcourakis, Tânia; Tsanaclis, Lolita; Bittencourt, Paulo R. M.

doi:10.1590/S0004-282X1991000200003

Abstracts

Quantitative measurements have indicated that heredity, cerebral damage, psycho-social aspects, ictal and inter-ictal phenomena and antiepileptic drugs may interfere in the cognitive dysfunction of epileptic patients. In the present study objective methods included immediate and late recall and recognition of pictures, Stroop test and auditory selection. Twenty patients with symptomatic localized epilepsy aged 17-52 years (27±10, mean ±sd) were compared to age and socially matched healthy controls. Patients were on therapeutic serum concentrations (25±12 m/mi) of phenobarbitone and had active epilepsy with 1.94 generalized tonic-clonic, 0.85 simple partial and 6.28 complex partial seizures monthly (means). Patients performed worse than controls in all 6 tests (p<0.05 to p<0.001), indicating a generalized cognitive deficit related to seizures and/or barbiturate therapy. We suggest further studies should be carried out in populations with uniform monotherapeutic regimens and epileptic syndromes in order to isolate factors related to the cognitive dysfunction of epileptic patients.

Estudos quantitativos anteriores têm demonstrado que hereditariedade, dano cerebral, aspectos psico-sociais, fenômenos ictais e interictais e drogas antiepilépticas interferem na disfunção cognitiva de pacientes epilépticos. Neste estudo os métodos objetivos incluiram memória e reconhecimento imediatos e tardio nas figuras, teste de Stroop e seleção auditiva. Vinte pacientes com epilepsia localizada sintomática entre 17 e 52 anos de idade (27±10, média ±d.p.) foram comparados a grupo controlado para idade e classe social. Os pacientes tinham concentrações terapêuticas (25±12 mg/ml) de fenobarbital e epilepsia ativa com 1,94 crises generalizadas tônico-clônicas, 0,85 parciais simples e 6,28 parciais complexas por mês (médias). Pacientes tiveram performances piores que controles em todos testes (P<0.05 a 0.001), indicando disfunção cognitiva generalizada relacionada com crises epilépticas e/ou tratamento com barbitúricos. Sugerimos que outros estudos com populações uniformes em regimes monoterapêuticos e síndromes epilépticas uniformes sejam realizados, para isolar fatores relacionados à disfunção cognitiva de pacientes epilépticos.

CONTENTS CONTEÚDO

Mônica M. Bigarella^I; Maria J. Mäder^I; Maribel P. Doro^I; Ana M. Gorz^II; Tânia Marcourakis^III; Lolita Tsanaclis^III; Paulo R. M. Bittencourt^II

^IUnidades de Psicologia Clínica

^IINeurologia

^IIIHospital Nossa Senhora das Graças, Curitiba, and Centro de Investigações em Neurologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo

SUMMARY

Quantitative measurements have indicated that heredity, cerebral damage, psycho-social aspects, ictal and inter-ictal phenomena and antiepileptic drugs may interfere in the cognitive dysfunction of epileptic patients. In the present study objective methods included immediate and late recall and recognition of pictures, Stroop test and auditory selection. Twenty patients with symptomatic localized epilepsy aged 17-52 years (27±10, mean ±sd) were compared to age and socially matched healthy controls. Patients were on therapeutic serum concentrations (25±12 m/mi) of phenobarbitone and had active epilepsy with 1.94 generalized tonic-clonic, 0.85 simple partial and 6.28 complex partial seizures monthly (means). Patients performed worse than controls in all 6 tests (p<0.05 to p<0.001), indicating a generalized cognitive deficit related to seizures and/or barbiturate therapy. We suggest further studies should be carried out in populations with uniform monotherapeutic regimens and epileptic syndromes in order to isolate factors related to the cognitive dysfunction of epileptic patients.

RESUMO

Estudos quantitativos anteriores têm demonstrado que hereditariedade, dano cerebral, aspectos psico-sociais, fenômenos ictais e interictais e drogas antiepilépticas interferem na disfunção cognitiva de pacientes epilépticos. Neste estudo os métodos objetivos incluiram memória e reconhecimento imediatos e tardio nas figuras, teste de Stroop e seleção auditiva. Vinte pacientes com epilepsia localizada sintomática entre 17 e 52 anos de idade (27±10, média ±d.p.) foram comparados a grupo controlado para idade e classe social. Os pacientes tinham concentrações terapêuticas (25±12 mg/ml) de fenobarbital e epilepsia ativa com 1,94 crises generalizadas tônico-clônicas, 0,85 parciais simples e 6,28 parciais complexas por mês (médias). Pacientes tiveram performances piores que controles em todos testes (P<0.05 a 0.001), indicando disfunção cognitiva generalizada relacionada com crises epilépticas e/ou tratamento com barbitúricos. Sugerimos que outros estudos com populações uniformes em regimes monoterapêuticos e síndromes epilépticas uniformes sejam realizados, para isolar fatores relacionados à disfunção cognitiva de pacientes epilépticos.

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Acknowledgment - The authors wish to thank Ms. J.P. Meister and Mrs. Maristela Gugelmin Calderari for secretarial assistance, and Mrs. M. Simioni for helpful comments.

Maria Joana Mäder - Unidade de Psicologia Clínica, Hospital Nossa Senhora das Graças - Rua Alcides Munhoz 433 - 80510 Curitiba PR- Brasil

1. Binnie CD, Kasteleijn-Nost, Smit AM, Wilkins AJ. Intertactions of epileptiform EEG discharges and cognition. Epilepsy Res. 1987, 1: 239.
2. Bittencourt PRM. Cerebral and cerebellar atrophy in patients with severe epilepsy: a preliminary report. In Oxley J, Janz D, Meinardi H (eds). : Chronic Toxicity of Anti-epileptic Drugs. New York : Raven Press, 1983, p 237.
3. Bittencourt PRM. Epilepsy in developing countries : Latin American aspects. In Laidlaw J, Richens A, Oxley J (eds). : Textbook Epilepsy. Ed 3, Edinburgh: Churchill-Livingstone, 1988, p 518.
4. Bittencourt PRM, Bigarella MM, Mäder MJ, Doro MP Gracia CM, Marcourakis TM. Cognitive functions of epileptic patients on monotherapeutic regimens and healthy controls. Epilepsia 1987, 28:S82.
5. Bittencourt PRM, Perucca E, Crema A. Cerebellar toxicity of antiepileptic drugs. In Blum K, Manzo L. (eds) : Neurotoxicology. New York: Marcel Dekker, 1984, p 223.
6. Bittencourt PRM, Richens A. Assessment of antiepileptic drug toxicity by eye movements. In Buser PA, Cobb WA, Okuma T, (eds) : Kyoto Symposia. EEG Clin Neuro-physiol 1982, S36:467. (Amsterdam : Elsevier, 1982).
7. Bittencourt PRM, Turner M. Epilepsy in Latin America. In Dam M, Gram L (eds) : International Epileptology, New York: Raven Press, in press.
8. Camfield AA, Chaplin S, Doyle AM, Schpiro CH, Cummings C, Lamfield PR. Side effects of phenobarbital in toddlers: behavioural land cognitive aspects. J. Pediatr 1980, 95:361.
9. Commission on Classification and Terminology of the ILAE,. Proposal for classification of epilepsies and epileptic syndromes. Epilepsia 1985, 26: 268.
10. Cull CA. Cognitive function and behaviour in children. In Trimble MR, Reynolds EH (eds) : Epilepsy Behaviour and Cognitive Function Chichester: John Wiley & Sons, 1988, p 97.
11. Cull CA, Trimble MR. Anticonvulsant benzodiazepines and performance. Internat Congress Symposium Series, Royal Soc Med 1985, 74:121.
12. Dodrill CB. Neuropsychology of epilepsy. In Filskov SB, Boll TS (eds): Handbook of Clinical Neuropsychology. New York : John Wiley, 1981, p 366.
13. Dodrill CB. Correlates of generalized tonic-clonic seizures with intellectual, neuropsychological, emotional, and social function in patients with epilepsy. Epilepsia 1986, 27:399.
14. Dodrill CB, Troupin AS. Effects of repeated administration of a comprehensive neuropsychological baterry among chronic epileptics. J Nerv Ment Dis 1974, 161:185.
15. Dodrill CB, Troupin AS. Psychotropic effect of carbamazepine in epilepsy: a double-blind comparison witih phenytoin. Neurology 1977, 27:1023.
16. Doro MP, Bigarella MM, Jader MJ, Gorz AM, Antoniuk SA, Silva GEG, Fonseca LC, Costa JC, Marcourakis TM, Tedros GMAS, Ferreira AS, Bittencourt PRM. Substituição de_t barbitúricos por fenitoína ou carbamazepina em epilepsia localizada sintomática: estudo prospectivo multicêntrico e controlado. Funções cognitivas. Arq Neuro-Psiquiat (São Paulo) 1988, 46(S)13.
17. Ellenberg JH, Hirtz DG, Nelson KB. Do seizures in children cause intellectual deterioration ? N Engl J Med 1986, 314:1085.
18. Hutt SJ, Jackson RM, Belsham A, Higgins G. Perceptual motor behaviour in relation to blood phenobarbitone level : a preliminary report. Dev Med Child Neurol 1968, 10:626.
19. Lennox WG. Brain injury, drugs and environment as causes of mental decay in epilepsy. Am J Psychiat 1942, 99:174.
20. MacLeod CM, Dekaban AS, Hunt E. Memory impairment in epileptic patients: selective effect of phenobarbitone concentration. Science 1978, 202:1102.
21. Ossertin J. Methods and problems in the assessment of cognitive function in epileptic patients. In Trimble MR, Reynolds EH (eds) : Epilepsy, Behaviour and Cognitive Function. Chichester: John Wiley & Sons, 1988, p 9.
22. Porter RJ. Recognizing and classifying epileptic seizures and epileptic syndromes. In Porter RJ. Theodore WH (eds) : Epilepsy. Neurol Clin 1986, 4:495.
23. Reynolds EH. Historical aspects. In Trimble MR, Reynolds EH (eds) : Epilepsy, Behaviour and Cognitive Function. Chichester : John Wiley & Sons, 1988, p 3.
24. Rimmer E, Richens A. Clinical pharmacology. In Laidlaw J, Richens A, Oxley (eds) : Textbook of Epilepsy. Ed 3. Edinburgh: Churchill-Livingstone, 1988, p 422.
25. Rodin E, Echmaltz S, Tuitly G. Intellectual functions of patients with childhood-onset epilepsy. Dev Med Child Neurol 1986, 28:25.
26. Smith DB. Anticonvulsants, seizures and performance: the Veteran's Administration experience. In Trimble MR, Reynolds EH (eds) : Epilepsy, Behaviour and Cognitive Function. Chichester: John Wiley & Sons, 1988, p 67.
27. Smith DB, Craft RB. VA Cooperative Study Group: differential neurotoxicity of four major anticonvulsants. Ann Neurol 1985, 18 : 119.
28. Thompson PJ. The effects of anticonvulsant drugs on the cognitive functioning of normal volunteers and patients with epilepsy. PhD Thesis, University of London. London, 1981.
29. Thompson P, Huppert FA, Trimble MR. Phenytoin and cognitive function: effects on normal volunteers and implications for epilepsy. BR J Clin Psychol 1981, 20:155.
30. Thompson PJ, Trimble MR. Sodium valproate and cognitive functioning in normal volunteers. Br Clin Pharmacol 1981, 12:819.
31. Thompson PJ, Trimble MR. Clozabam and cognitive functions: effects in healthy volunteers. In Clobazam : Internat Congress Symposium Series, Royal Soc Med 1981, 43:33.
32. Thompson PJ, Trimble MR, Comparative effects of anticonvulsant drugs on cognitive functioning. Br J Clin Pract 1982, 18(S):154.
33. Thompson PJ, Trimble MR. Anticonvulsant drugs and cognitive functions. Epilepsia 1982, 33:531.
34. Thompson PJ, Trimble MR. Anticonvulsant serum levels: relationship to impairments of cognitive functioning. J Neurol Neurosurg Psychiat 1983, 46:227.
35. Trimble MR. Anticonvulsivant drugs and cognitive function : a review of the literature. Epilepsia 1987, 28(S3):537.
36. Trimble MR. Anticonvulsant drugs: mood and cognitive function. In Trimble MR, Reynold EH (eds) : Epilepsy, Behaviour and Cognitive Function Chichester: John Wiley & Sons, 1988, p 135.
37. Trimble MR, Reynolds EH. Anticonvulsant drugs and mental symptoms. Psychol Med 1976, 6:169.
38. Trimble MR, Thompson PJ. Anticonvulsant drugs, cognitive functions and behaviour. Epilepsia 1983, 24(S1):55.
39. Vining EPG. Cognitive dysfunction associated with antiepileptic drug therapy. Epilepsia 1987, 28(S2):518.

Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls

Função cognitiva de pacientes epilépticos em monoterapia com fenobarbital e contrôles.

Publication Dates

Publication in this collection
22 Feb 2011
Date of issue
June 1991

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

[1] 1. Binnie CD, Kasteleijn-Nost, Smit AM, Wilkins AJ. Intertactions of epileptiform EEG discharges and cognition. Epilepsy Res. 1987, 1: 239.

[2] 2. Bittencourt PRM. Cerebral and cerebellar atrophy in patients with severe epilepsy: a preliminary report. In Oxley J, Janz D, Meinardi H (eds). : Chronic Toxicity of Anti-epileptic Drugs. New York : Raven Press, 1983, p 237.

[3] 3. Bittencourt PRM. Epilepsy in developing countries : Latin American aspects. In Laidlaw J, Richens A, Oxley J (eds). : Textbook Epilepsy. Ed 3, Edinburgh: Churchill-Livingstone, 1988, p 518.

[4] 4. Bittencourt PRM, Bigarella MM, Mäder MJ, Doro MP Gracia CM, Marcourakis TM. Cognitive functions of epileptic patients on monotherapeutic regimens and healthy controls. Epilepsia 1987, 28:S82.

[5] 5. Bittencourt PRM, Perucca E, Crema A. Cerebellar toxicity of antiepileptic drugs. In Blum K, Manzo L. (eds) : Neurotoxicology. New York: Marcel Dekker, 1984, p 223.

[6] 6. Bittencourt PRM, Richens A. Assessment of antiepileptic drug toxicity by eye movements. In Buser PA, Cobb WA, Okuma T, (eds) : Kyoto Symposia. EEG Clin Neuro-physiol 1982, S36:467. (Amsterdam : Elsevier, 1982).

[7] 7. Bittencourt PRM, Turner M. Epilepsy in Latin America. In Dam M, Gram L (eds) : International Epileptology, New York: Raven Press, in press.

[8] 8. Camfield AA, Chaplin S, Doyle AM, Schpiro CH, Cummings C, Lamfield PR. Side effects of phenobarbital in toddlers: behavioural land cognitive aspects. J. Pediatr 1980, 95:361.

[9] 9. Commission on Classification and Terminology of the ILAE,. Proposal for classification of epilepsies and epileptic syndromes. Epilepsia 1985, 26: 268.

[10] 10. Cull CA. Cognitive function and behaviour in children. In Trimble MR, Reynolds EH (eds) : Epilepsy Behaviour and Cognitive Function Chichester: John Wiley & Sons, 1988, p 97.

[11] 11. Cull CA, Trimble MR. Anticonvulsant benzodiazepines and performance. Internat Congress Symposium Series, Royal Soc Med 1985, 74:121.

[12] 12. Dodrill CB. Neuropsychology of epilepsy. In Filskov SB, Boll TS (eds): Handbook of Clinical Neuropsychology. New York : John Wiley, 1981, p 366.

[13] 13. Dodrill CB. Correlates of generalized tonic-clonic seizures with intellectual, neuropsychological, emotional, and social function in patients with epilepsy. Epilepsia 1986, 27:399.

[14] 14. Dodrill CB, Troupin AS. Effects of repeated administration of a comprehensive neuropsychological baterry among chronic epileptics. J Nerv Ment Dis 1974, 161:185.

[15] 15. Dodrill CB, Troupin AS. Psychotropic effect of carbamazepine in epilepsy: a double-blind comparison witih phenytoin. Neurology 1977, 27:1023.

[16] 16. Doro MP, Bigarella MM, Jader MJ, Gorz AM, Antoniuk SA, Silva GEG, Fonseca LC, Costa JC, Marcourakis TM, Tedros GMAS, Ferreira AS, Bittencourt PRM. Substituição de_t barbitúricos por fenitoína ou carbamazepina em epilepsia localizada sintomática: estudo prospectivo multicêntrico e controlado. Funções cognitivas. Arq Neuro-Psiquiat (São Paulo) 1988, 46(S)13.

[17] 17. Ellenberg JH, Hirtz DG, Nelson KB. Do seizures in children cause intellectual deterioration ? N Engl J Med 1986, 314:1085.

[18] 18. Hutt SJ, Jackson RM, Belsham A, Higgins G. Perceptual motor behaviour in relation to blood phenobarbitone level : a preliminary report. Dev Med Child Neurol 1968, 10:626.

[19] 19. Lennox WG. Brain injury, drugs and environment as causes of mental decay in epilepsy. Am J Psychiat 1942, 99:174.

[20] 20. MacLeod CM, Dekaban AS, Hunt E. Memory impairment in epileptic patients: selective effect of phenobarbitone concentration. Science 1978, 202:1102.

[21] 21. Ossertin J. Methods and problems in the assessment of cognitive function in epileptic patients. In Trimble MR, Reynolds EH (eds) : Epilepsy, Behaviour and Cognitive Function. Chichester: John Wiley & Sons, 1988, p 9.

[22] 22. Porter RJ. Recognizing and classifying epileptic seizures and epileptic syndromes. In Porter RJ. Theodore WH (eds) : Epilepsy. Neurol Clin 1986, 4:495.

[23] 23. Reynolds EH. Historical aspects. In Trimble MR, Reynolds EH (eds) : Epilepsy, Behaviour and Cognitive Function. Chichester : John Wiley & Sons, 1988, p 3.

[24] 24. Rimmer E, Richens A. Clinical pharmacology. In Laidlaw J, Richens A, Oxley (eds) : Textbook of Epilepsy. Ed 3. Edinburgh: Churchill-Livingstone, 1988, p 422.

[25] 25. Rodin E, Echmaltz S, Tuitly G. Intellectual functions of patients with childhood-onset epilepsy. Dev Med Child Neurol 1986, 28:25.

[26] 26. Smith DB. Anticonvulsants, seizures and performance: the Veteran's Administration experience. In Trimble MR, Reynolds EH (eds) : Epilepsy, Behaviour and Cognitive Function. Chichester: John Wiley & Sons, 1988, p 67.

[27] 27. Smith DB, Craft RB. VA Cooperative Study Group: differential neurotoxicity of four major anticonvulsants. Ann Neurol 1985, 18 : 119.

[28] 28. Thompson PJ. The effects of anticonvulsant drugs on the cognitive functioning of normal volunteers and patients with epilepsy. PhD Thesis, University of London. London, 1981.

[29] 29. Thompson P, Huppert FA, Trimble MR. Phenytoin and cognitive function: effects on normal volunteers and implications for epilepsy. BR J Clin Psychol 1981, 20:155.

[30] 30. Thompson PJ, Trimble MR. Sodium valproate and cognitive functioning in normal volunteers. Br Clin Pharmacol 1981, 12:819.

[31] 31. Thompson PJ, Trimble MR. Clozabam and cognitive functions: effects in healthy volunteers. In Clobazam : Internat Congress Symposium Series, Royal Soc Med 1981, 43:33.

[32] 32. Thompson PJ, Trimble MR, Comparative effects of anticonvulsant drugs on cognitive functioning. Br J Clin Pract 1982, 18(S):154.

[33] 33. Thompson PJ, Trimble MR. Anticonvulsant drugs and cognitive functions. Epilepsia 1982, 33:531.

[34] 34. Thompson PJ, Trimble MR. Anticonvulsant serum levels: relationship to impairments of cognitive functioning. J Neurol Neurosurg Psychiat 1983, 46:227.

[35] 35. Trimble MR. Anticonvulsivant drugs and cognitive function : a review of the literature. Epilepsia 1987, 28(S3):537.

[36] 36. Trimble MR. Anticonvulsant drugs: mood and cognitive function. In Trimble MR, Reynold EH (eds) : Epilepsy, Behaviour and Cognitive Function Chichester: John Wiley & Sons, 1988, p 135.

[37] 37. Trimble MR, Reynolds EH. Anticonvulsant drugs and mental symptoms. Psychol Med 1976, 6:169.

[38] 38. Trimble MR, Thompson PJ. Anticonvulsant drugs, cognitive functions and behaviour. Epilepsia 1983, 24(S1):55.

[39] 39. Vining EPG. Cognitive dysfunction associated with antiepileptic drug therapy. Epilepsia 1987, 28(S2):518.