Vigabatrin: clinical evidence supporting rational polytherapy in management of uncontrolled seizures.

Monotherapy is the policy for management of patients with epilepsy. With increasing knowledge of the biology of epilepsy and of the modes of action of antiepileptic drugs (AEDs), this concept must be reevaluated. When monotherapy fails to control seizures, subsequent treatment should be based on "rational pharmacology," taking into consideration the mode of action of the drugs, to provide improved efficacy with maintained tolerance and ease of administration. Introduction of vigabatrin (VGB) as a new AED calls for just such a reevaluation. VGB is an enzyme-activated irreversible inhibitor of gamma-aminobutyric acid (GABA)-transaminase that increases brain and cerebrospinal (CSF) GABA concentrations in animals and humans. It has limited efficacy in the classic animal seizure screening tests, but in many clinical studies has halved the incidence of seizures in approximately 50% of patients, especially those with partial epilepsies. We evaluated the efficacy of VGB in "socially integrated and active outpatients" as a likely subset to demonstrate any advantage of rational polytherapy. The criteria for this evaluation included the effects on seizure frequency, patient tolerability, and cognitive performance in a battery of psychometric tests. Fourteen of the 19 patients (73%) completing the study had > 50% reduction in seizure frequency, and 10 of 19 (52%) had > 70% reduction in seizure frequency. Tolerability appeared good; somnolence was the most frequent adverse event. Three patients complained of a worsening of their seizures, 1 with an increase in frequency and 2 with development of myoclonic jerks not previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbamazepine and phenytoin in epilepsies refractory to barbiturates: efficacy, toxicity and mental function.

A group of 51 patients with chronic cryptogenic or symptomatic localized epilepsy refractory to therapy with barbiturates underwent progressive substitution with phenytoin or carbamazepine, in standardized and randomized fashion. After drug changes were completed two thirds of the patients remained seizure free during a period of 6 months. A clearer effect of phenytoin and carbamazepine was seen on secondary generalized than on partial seizures. The frequency of severe side effects decreased after the change to phenytoin and carbamazepine. The group on carbamazepine improved in immediate and late recall, and in immediate and late recognition of pictures. The group on phenytoin improved significantly in the Stroop test. Patients changed to phenytoin, but not those changed to carbamazepine, became significantly more aggressive, anxious and depressive than when on phenobarbital, as measured by subjective scales. The results indicate that patients should not be considered refractory to antiepileptic drug therapy while on barbiturates. Cognitive dysfunction and mood changes observed in epilepsy may be temporary and dependent on the presence of seizures and/or on use of barbiturates.

Cognitive functions, epileptic syndromes and antiepileptic drugs.

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 micrograms/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 poly-therapeutic drug regimen must be multifactorial, and that future studies need to control for all possible variables in order to achieve meaningful results.

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

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 mu/ml) 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 less than 0.05 to p less than 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.

Comprometimento psicomotor por anestésicos locais: estudo prospectivo visando anestesia ambulatorial / Psychomotor involvement by local anesthetics: prospective study aiming the ambulatorial anesthesia

A normalizaçäo das funçöes psicomotoras ao nível de normalidade tem sido apontado como critério de alta do paciente externo (ambulatorial). Objetiva-se avaliar prospectivamente o comprometimento das funçöes psicomotoras (intensidade e duraçäo de pacientes submetidos a anestesia com a lidocaína e a bupivacaína. Foram estudadas as variaçöes de testes psicomotores em 24 pacientes, todos ASA I, de ambos os sexos, programados para cirurgias sobre o membro superior, após a aplicaçäo de doses supramaximais das drogas, em bloqueios do plexo braquial por via axiliar, comparado a parâmetros controles estabelecidos antes da anestesia. Os testes que avaliaram Memória, Atençäo, Vigilância, Percepçäo Visual, Organizaçäo no Espaço, Rapidez de Movimentos Horizontais e Verticais, Percepçäo Auditiva, Habilidade Manual, Cálculos, Equilíbrio Estático e Dinâmico, Controle Psotural, Noçäo de Posiçäo Segmentar, Apraxia Ideomotora, Cogniçäo, Verbalizaçäo Abstrata, Lógica e Coordenaçäo Dinâmica Manual, demonstraram que näo houve deterioraçäo significativa nas habilidades, exceto na Memória Visual com o grupo da lidocaína aos 137 + ou - 27,6 após a execuçäo do bloqueio. Os elementos que participam no complexo da Memória Visual estäo, também, presentes em outros testes que näo demonstram modificaçöes significativas. Säo aventadas hipóteses emocionais e farmacológicas para esta ocorrência. Quanto ao comportamento Global das funçöes mais elaboradas do Sistema Nervoso Central, näo houve variaçäo significativa mesmo no momento teórico de maior nível plasmático das drogas, o que permite deduzir que, do ponto de vista da psicomotricidade, näo há contra-indicaçäo absoluta de alta precoce dos pacientes submetidos ao bloqueio do plexo braquial por via axilar, com bupivacaína e lidocaína, ainda que o bloqueio esteja atuando. Mesmo assim, recomenda-se a utilizaçäo de alguns testes da anestesia e antes da alta, p ara evitar algumas variaçöes para pior, de ordem absolutamente individual