Cognitive functions, epileptic syndromes and antiepileptic drugs

Bittencourt, Paulo R. M.; Mader, Maria Joana; Bigarella, Monica M.; Dóro, Maribel P.; Gorz, Ana M.; Marcourakis, Tania M.; Ferreira, Zulma S.

doi:10.1590/S0004-282X1992000100005

Abstracts

Cognitive function of patients on monotherapy specific for their epileptic syndrome has been studied infrequently. We evaluated 7 patients with symptomatic localised epilepsies (SEL) on phenytoin aged 30±12 (mean±standard deviation) years, 8 with idiopathic generalised epilepsies on sodium valproate aged 18±4 years, 16 with SEL on carbamazepine aged 28±11 years, and 35 healthy controls aged 27±11 years. All subjects were of normal intelligence, educated appropriately to age, and led productive lives in the community. Two of the patients on carbamazepine and one on valproate had less than five partial, absence or myoclonic seizures monthly, the remaining were controlled. Carbamazepine serum concentrations were 12±5 ug/ml, phenytoin were 23±7, and valproate were 62±23 (mean±sd). Tests included immediate recall and recognition for pictures, Stroop test, delayed recall and recognition of pictures. Patients on phenytoin and valproate performed significantly worse than controls on immediate recall, and patients on carbamazepine performed significantly worse than controls in Stroop test (p<0,01). The results indicate relatively minor effects of the epileptic syndromes and of phenytoin, carbamazepine and valproate on cognition of patients with controlled epilepsy leading productive lives in the community. We conclude that the cognitive deficit found in chronic epileptic patients on polytherapeutic drug regimen must be multifactorial, and that future studies need to control for all possible variables in order to achieve meaningul results.

epilepsy; cognitive disorders; neuropsychology; phenytoin; carbamazepine; sodium valproate

Função cognitiva de placientes em monoterapia específica para síndrome epiléptica tem sido pouco avaliada. Estudamos: 7 pacientes com epilepsias localizadas sintomáticas (SEL) utilizando fenitoína, com 30±12 (média ± desvio padrão) anos de idade; 8 com epilepsias generalizadas idiopáticas utilizando valproato de sódio, com 18±4 anos; 16 com SEL utilizando carbamazepina, com 28±11 anos; 35 controles sadios, com 27±11 anos. Todos tinham inteligência normal, educação apropriada para a idade e vidas produtivas na sociedade. Dois dos pacientes utilizando carbamazepina e um valproato de sódio tinham menos de 5 crises parciais, de ausência ou mioclônicas ao mês. Os outros pacientes tinham crises controladas há mais de 6 meses. As concentrações séricas de carbamazepina, fenitoína e valproato de sódio foram 12±5, 23±7 e 62±23 ug/ml. Os testes incluíram memória e reconhecimento imediato e tardio de figuras e Stroop. Pacientes do grupo de fenitoína e valproato tiveram performance pior que controles em memória imediata; o grupo de carbamazepina foi pior que controles no teste de Stroop (p<0.01). Os resultados indicam efeitos discretos das síndromes epilépticas, de fenitoína, carbamazepina e valproato de sódio na cognição de pacientes com epilepsia eminentemente controlada e vida produtiva na comunidade. O déficit de pacientes com epilepsia crônica sob regimes politerapêuticos deve ser multifatorial. Estudos futuros devem controlar, em seu planejamento, fatores causais possíveis para que seus resultados sejam relevantes.

epilepsia; desordens cognitivas; neuropsicologia; fenitoína; carbamazepina; valproato de sódio

Paulo R. M. Bittencourt^I; Maria Joana Mader^II; Monica M. Bigarella^II; Maribel P. Dóro^II; Ana M. Gorz^I; Tania M. Marcourakis^III; Zulma S. Ferreira^III

^IClinical Neurology and Clinical Psychology

^IIUnits, Hospital N.Sra. das Graças, Curitiba; and Neurology Investigation Center

^IIIUniversity of São Paulo, São Paulo

SUMMARY

Cognitive function of patients on monotherapy specific for their epileptic syndrome has been studied infrequently. We evaluated 7 patients with symptomatic localised epilepsies (SEL) on phenytoin aged 30±12 (mean±standard deviation) years, 8 with idiopathic generalised epilepsies on sodium valproate aged 18±4 years, 16 with SEL on carbamazepine aged 28±11 years, and 35 healthy controls aged 27±11 years. All subjects were of normal intelligence, educated appropriately to age, and led productive lives in the community. Two of the patients on carbamazepine and one on valproate had less than five partial, absence or myoclonic seizures monthly, the remaining were controlled. Carbamazepine serum concentrations were 12±5 ug/ml, phenytoin were 23±7, and valproate were 62±23 (mean±sd). Tests included immediate recall and recognition for pictures, Stroop test, delayed recall and recognition of pictures. Patients on phenytoin and valproate performed significantly worse than controls on immediate recall, and patients on carbamazepine performed significantly worse than controls in Stroop test (p<0,01). The results indicate relatively minor effects of the epileptic syndromes and of phenytoin, carbamazepine and valproate on cognition of patients with controlled epilepsy leading productive lives in the community. We conclude that the cognitive deficit found in chronic epileptic patients on polytherapeutic drug regimen must be multifactorial, and that future studies need to control for all possible variables in order to achieve meaningul results.

Key words: epilepsy, cognitive disorders, neuropsychology, phenytoin, carbamazepine, sodium valproate.

RESUMO

Função cognitiva de placientes em monoterapia específica para síndrome epiléptica tem sido pouco avaliada. Estudamos: 7 pacientes com epilepsias localizadas sintomáticas (SEL) utilizando fenitoína, com 30±12 (média ± desvio padrão) anos de idade; 8 com epilepsias generalizadas idiopáticas utilizando valproato de sódio, com 18±4 anos; 16 com SEL utilizando carbamazepina, com 28±11 anos; 35 controles sadios, com 27±11 anos. Todos tinham inteligência normal, educação apropriada para a idade e vidas produtivas na sociedade. Dois dos pacientes utilizando carbamazepina e um valproato de sódio tinham menos de 5 crises parciais, de ausência ou mioclônicas ao mês. Os outros pacientes tinham crises controladas há mais de 6 meses. As concentrações séricas de carbamazepina, fenitoína e valproato de sódio foram 12±5, 23±7 e 62±23 ug/ml. Os testes incluíram memória e reconhecimento imediato e tardio de figuras e Stroop. Pacientes do grupo de fenitoína e valproato tiveram performance pior que controles em memória imediata; o grupo de carbamazepina foi pior que controles no teste de Stroop (p<0.01). Os resultados indicam efeitos discretos das síndromes epilépticas, de fenitoína, carbamazepina e valproato de sódio na cognição de pacientes com epilepsia eminentemente controlada e vida produtiva na comunidade. O déficit de pacientes com epilepsia crônica sob regimes politerapêuticos deve ser multifatorial. Estudos futuros devem controlar, em seu planejamento, fatores causais possíveis para que seus resultados sejam relevantes.

Palavras chave: epilepsia, desordens cognitivas, neuropsicologia, fenitoína, carbamazepina, valproato de sódio.

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Full text available only in PDF format.

Acknowledgement The authors wish to thank Ms. M. G. Calderarl and Mrs. M. Simioni for secretarial assistance and helpful comments.

Dr. Paulo R. M. Bittencourt Hospital Nossa Senhora das Graças - Rua Alcides Munhoz 433 -80510 Curitiba PR - Brasil.

1. Aldenkamp AP, Alpherts WCJ, Moerland MC, Ottevanger N, Van Parys JAP. Controlled release carbamazepine: cognitive side effects in patients with epilepsy. Epilepsia 1987, 28:507-514.
2. Aman MG, Werry JS, Paxton JW, Turbott SH. Effects of sodium valproate on psychomotor performance in children as a function of dose, fluctuation in concentration and diagnosis, Epilepsia 1987, 28:115-124.
3. Bigarella MM, Mader MJ, Doro MP, Gorz AM, Marcourakis T, Tsanaclis L, Bittencourt PRM. Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls. Arq Neuropsiquiatr 1991, 49:136-141.
4. Binnie CD, Kasteleijn-Nolst, Trenité DGA, Smith AM, Wilkins AJ. Interactions of epileptiform EEG discharges and cognition. Epilepsy Res 1987, 239-245.
5. 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 Antiepileptic Drugs. New York: Raven Press, 1983, p 237-246.
6. Bittencourt PRM. Epilepsy in developing countries: Latin American aspects. In Laidlaw J, Richens A, Oxley J (eds): Textbook of Epilepsy. Ed 3. Edinburgh: Churchill-Livingstone 1988, p 518-527.
7. Bittencourt PRM, Perucca E, Crema A. Cerebellar toxicity of antiepileptic drugs. In Blum K, Manzo L (eds): Neurotoxicology. New York: Marcel Dekker 1984, p 233-250.
8. Bittencourt PRM, Richens A. Assessment of antiepileptic drug toxicity by eye movements. In Buser PA, Cobb, WA, Okuma T (eds): Kyoto Symposia, EEG and Clinical Neurophysiology, Suppl 36, Amsterdam: Elsevier 1982, p 467-481.
9. Bittencourt PRM, Turner M. Epilepsy in Latin America. In Dam M Gram L (eds): International Epileptology, New York: Raven Press 1991, p 807-820.
10. Camfield AA, Chaplin S, Doyle AM. Side effects of phenobarbital in toddlers: behavioural and cognitive aspects. J Pediatrics 1980, 95:361-365.
11. Comission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981, 22:489-501.
12. Commission on Classification and Terminology of the ILAE. Proposal for classification of epilepsies and epileptic syndromes. Epilepsia 1985, 26:268-278.
13. Cull CA. Cognitive function and behaviour in children. In Trimble MR, Reynolds EH (eds): Epilepsy, Behaviour and Cognitive Function Chichester: John Wiley and Sons 1988. p 97-111.
14. Cull CA, Trimble MR. Anticonvulsant benzodiazepines and performance. Internat Congress Symposium Series, Royal Soc Med 1985, 74:121-128. London: Academic Press.
15. Dodrill CB. Correlates of generalized tonic-clonic seizures with intellectual, neuropsychological, emotional, and social function in patients with epilepsy. Epilepsia 1986, 27:399-411.
36. Foster AC, Fagg GE. Taking apart NMDA receptors, Nature 1987, 329:395-396.
17. Gallassi R, Morreale A, Lorusso S, Ferrari M, Procaccianti G, Lugaressi E, Baruzzi A. Cognitive effects of phenytoin during monotheraphy and after withdrawl. Acta Neurol Scand 1987, 75:258-261.
18. Hermann BP, Wyler AR, Richey ET, Rea JH. Memory functions and verbal learning ability in patients with complex partial seizures of temporal lobe origin. Epilepsia 1987, 28:547-554.
19. MacLeod CM, Dekaban AS, Hunt E. Memory impairment in epileptic patients: selective effect of phenobarbitone concentration. Science 1978, 202:1102-1104.
20. Meador KJ, Loring DW, Huh K, Gallagher BB, King DW. Comparative cognitive effects of anticonvulsants. Neurology 1990, 40:391-394.
21. Ossertin J. Methods and problems in the assessment of cognitive function in epileptic patients. In Trimble MR, Reynolds EM (eds): Epilepsy, Behaviour and Cognitive Function, Chichester: John Wiley & Sons 1988, p 9-26.
22. Rimmer E, Richens A. Clinical pharmacology. In Laidlaw J, Richens A, Oxley .1 (eds): Textbook of Epilepsy. Ed 3. Edinburgh: Churchill-Livingstone 1988, p 422-483.
23. Rodin E, Schmaltz S, Tuitly G. Intellectual functions of patients with childhood-onset epilepsy. Dev Med Child Neurol 1986, 28:25-33.
24. 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 67-78.
25. Smith DB, Craft RB. VA Cooperative Study Group. Differential neurotoxicity of four major anticonvulsants (Abstr). Ann Neurol 1985, 18:119.
26. Thompson PJ, Huppert FA, Trimble MR. Phenytoin and cognitive function: effects on normal volunteers and implications for epilepsy. Br J Clin Psychol 1981, 20:155-162.
27. Thompson PJ, Trimble MR. Sodium valproate and cognitive functioning in normal volunters. Br J Clin Pharmacol 1981, 12:179-182.
28. Thompson PJ, Trimble MR. Clobazam and cognitive functions: effects in healthy volunteers. In Clobazam Internat Congress Symposium Series, Royal Soc Med 1981, 43:33-38. London: Academic Press.
29. Thompson PJ, Trimble MR. Anticonvulsant drugs and cognitive functions. Epilepsia 1982, 33:531-544.
30. Thompson PJ, Trimble MR. Comparative effects of anticonvulsant drugs on cognitive functioning. Br J Clin Practice 1982, 18 (Suppl): 154-156.
31. Thompson PJ, Trimble MR. Anticonvulsant serum levels: relationship to impairments of cognitive functioning. J Neurol Neurosurg Psychiatry 1983, 46:227-233.
32. Vining EPG. Cognitive dysfunction associated with antiepileptic drug therapy. Epilepsia 1987, 28 (Suppl 2): S18-S22.

Cognitive functions, epileptic syndromes and antiepileptic drugs

Funções cognitiva, síndromes epilépticas e drogas antiepilépticas

Publication Dates

Publication in this collection
22 Feb 2011
Date of issue
Mar 1992

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

[1] 1. Aldenkamp AP, Alpherts WCJ, Moerland MC, Ottevanger N, Van Parys JAP. Controlled release carbamazepine: cognitive side effects in patients with epilepsy. Epilepsia 1987, 28:507-514.

[2] 2. Aman MG, Werry JS, Paxton JW, Turbott SH. Effects of sodium valproate on psychomotor performance in children as a function of dose, fluctuation in concentration and diagnosis, Epilepsia 1987, 28:115-124.

[3] 3. Bigarella MM, Mader MJ, Doro MP, Gorz AM, Marcourakis T, Tsanaclis L, Bittencourt PRM. Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls. Arq Neuropsiquiatr 1991, 49:136-141.

[4] 4. Binnie CD, Kasteleijn-Nolst, Trenité DGA, Smith AM, Wilkins AJ. Interactions of epileptiform EEG discharges and cognition. Epilepsy Res 1987, 239-245.

[5] 5. 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 Antiepileptic Drugs. New York: Raven Press, 1983, p 237-246.

[6] 6. Bittencourt PRM. Epilepsy in developing countries: Latin American aspects. In Laidlaw J, Richens A, Oxley J (eds): Textbook of Epilepsy. Ed 3. Edinburgh: Churchill-Livingstone 1988, p 518-527.

[7] 7. Bittencourt PRM, Perucca E, Crema A. Cerebellar toxicity of antiepileptic drugs. In Blum K, Manzo L (eds): Neurotoxicology. New York: Marcel Dekker 1984, p 233-250.

[8] 8. Bittencourt PRM, Richens A. Assessment of antiepileptic drug toxicity by eye movements. In Buser PA, Cobb, WA, Okuma T (eds): Kyoto Symposia, EEG and Clinical Neurophysiology, Suppl 36, Amsterdam: Elsevier 1982, p 467-481.

[9] 9. Bittencourt PRM, Turner M. Epilepsy in Latin America. In Dam M Gram L (eds): International Epileptology, New York: Raven Press 1991, p 807-820.

[10] 10. Camfield AA, Chaplin S, Doyle AM. Side effects of phenobarbital in toddlers: behavioural and cognitive aspects. J Pediatrics 1980, 95:361-365.

[11] 11. Comission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981, 22:489-501.

[12] 12. Commission on Classification and Terminology of the ILAE. Proposal for classification of epilepsies and epileptic syndromes. Epilepsia 1985, 26:268-278.

[13] 13. Cull CA. Cognitive function and behaviour in children. In Trimble MR, Reynolds EH (eds): Epilepsy, Behaviour and Cognitive Function Chichester: John Wiley and Sons 1988. p 97-111.

[14] 14. Cull CA, Trimble MR. Anticonvulsant benzodiazepines and performance. Internat Congress Symposium Series, Royal Soc Med 1985, 74:121-128. London: Academic Press.

[15] 15. Dodrill CB. Correlates of generalized tonic-clonic seizures with intellectual, neuropsychological, emotional, and social function in patients with epilepsy. Epilepsia 1986, 27:399-411.

[16] 36. Foster AC, Fagg GE. Taking apart NMDA receptors, Nature 1987, 329:395-396.

[17] 17. Gallassi R, Morreale A, Lorusso S, Ferrari M, Procaccianti G, Lugaressi E, Baruzzi A. Cognitive effects of phenytoin during monotheraphy and after withdrawl. Acta Neurol Scand 1987, 75:258-261.

[18] 18. Hermann BP, Wyler AR, Richey ET, Rea JH. Memory functions and verbal learning ability in patients with complex partial seizures of temporal lobe origin. Epilepsia 1987, 28:547-554.

[19] 19. MacLeod CM, Dekaban AS, Hunt E. Memory impairment in epileptic patients: selective effect of phenobarbitone concentration. Science 1978, 202:1102-1104.

[20] 20. Meador KJ, Loring DW, Huh K, Gallagher BB, King DW. Comparative cognitive effects of anticonvulsants. Neurology 1990, 40:391-394.

[21] 21. Ossertin J. Methods and problems in the assessment of cognitive function in epileptic patients. In Trimble MR, Reynolds EM (eds): Epilepsy, Behaviour and Cognitive Function, Chichester: John Wiley & Sons 1988, p 9-26.

[22] 22. Rimmer E, Richens A. Clinical pharmacology. In Laidlaw J, Richens A, Oxley .1 (eds): Textbook of Epilepsy. Ed 3. Edinburgh: Churchill-Livingstone 1988, p 422-483.

[23] 23. Rodin E, Schmaltz S, Tuitly G. Intellectual functions of patients with childhood-onset epilepsy. Dev Med Child Neurol 1986, 28:25-33.

[24] 24. 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 67-78.

[25] 25. Smith DB, Craft RB. VA Cooperative Study Group. Differential neurotoxicity of four major anticonvulsants (Abstr). Ann Neurol 1985, 18:119.

[26] 26. Thompson PJ, Huppert FA, Trimble MR. Phenytoin and cognitive function: effects on normal volunteers and implications for epilepsy. Br J Clin Psychol 1981, 20:155-162.

[27] 27. Thompson PJ, Trimble MR. Sodium valproate and cognitive functioning in normal volunters. Br J Clin Pharmacol 1981, 12:179-182.

[28] 28. Thompson PJ, Trimble MR. Clobazam and cognitive functions: effects in healthy volunteers. In Clobazam Internat Congress Symposium Series, Royal Soc Med 1981, 43:33-38. London: Academic Press.

[29] 29. Thompson PJ, Trimble MR. Anticonvulsant drugs and cognitive functions. Epilepsia 1982, 33:531-544.

[30] 30. Thompson PJ, Trimble MR. Comparative effects of anticonvulsant drugs on cognitive functioning. Br J Clin Practice 1982, 18 (Suppl): 154-156.

[31] 31. Thompson PJ, Trimble MR. Anticonvulsant serum levels: relationship to impairments of cognitive functioning. J Neurol Neurosurg Psychiatry 1983, 46:227-233.

[32] 32. Vining EPG. Cognitive dysfunction associated with antiepileptic drug therapy. Epilepsia 1987, 28 (Suppl 2): S18-S22.