During the recent years, a significant number of anti-epileptic drugs have been approved for prescription in different countries. In addition, some other promising drugs are in various stages of development. Soon after each drug has found its place in the therapeutic arsenal, pregnancies with exposure occur, with an increased risk of birth defect and developmental disturbances. As regards the possible teratogenic effect of the new anti-epileptic drugs, apart some individual reports we have only the results of pre-clinical toxicological studies which are difficult to extrapolate to the human situation, because of the well-known interspecies differences in pharmacokinetics and pharmacodynamics. Furthermore, combinations of anti-epileptic drugs are not tested pre-clinically while these new drugs are prescribed as add-on medication. So, metabolic interactions between individual components of such drug combinations may induce unexpected teratogenic effects. Also as for the teratogenic effects of the old drugs many questions have still to be defined. The most common and more important are which anti-epileptic drugs or combination of drugs is most safe for a particular woman with epilepsy and if there is an association between single anti-epileptic drugs and specific malformations. The reason is that none of the available reports to date have studied a sufficient number of women with epilepsy exposed to anti-epileptic drug monotherapy during pregnancy. Other questions concern dose-effect relationships, a universally accepted definition of major and minor malformations, and the lack of a thorough, exhaustive evaluation of the other risk factors, apart from the drugs. All these questions need to be ascertained for both the old and the new anti-epileptic drugs. Owing to these considerations, in 1998 an European Register of anti-epileptic drugs and pregnancy was instituted. The primary objective of the study is to evaluate and determine the degree of safety, with respect to the human foetus, of anti-epileptic drugs with reference to both old and new, and to individual drugs and drugs in combination. Secondary objectives are to establish the pattern of abnormalities, if any, associated with anti-epileptic drugs individually and in combination, to delineate drug-specific syndromes, if any, to evaluate dose-effect relationships. Tertiary objectives are to provide references data for use in pre-pregnancy counselling, and for development of guidelines. The evaluation of other etiological risk factors is also considered.
Studies examining the use of vigabatrin as monotherapy for the treatment of epilepsy are relatively scarce, and of the few that have been reported, only two were of sufficient size to provide definitive data.In both trials, vigabatrin was compared with carbamazepine for efficacy and safety. In one of these studies, carbamazepine was found to be more effective than vigabatrin in reducing seizure frequency, and the two were found to be comparably efficacious in the other study. What differed significantly, however, was vigabatrin9s favorable safety profile. Vigabatrin appears to be a reasonable choice for single-drug therapy in the treatment of certain types of seizures. In other patients, it remains useful as an adjunct to other antiepileptic drugs. NEUROLOGY 1996;47(Suppl 1): S2-S5
174 subjects suffering from late onset epilepsy were examined. The incidence of cerebral atrophy, defined with objective criteria on CT scans by means of a comparative analysis with a matched for age control group was 37.9%. Head traumas, cerebrovascular disorders and alcoholism were the presumed etiological factors in most of the cases while in 25 subjects (20%) the etiology of cerebral atrophy remained unknown ("cryptogenous atrophy"). Clinical profil, psychometric performance and EEG characteristics of these subjects were investigated and compared with the remainder groups of late-onset epileptics. The results obtained show that the subjects with cryptogenous atrophy behave, as regard the features considered, as the late-onset epileptics with normal CT but present an higher familial prevalence for epilepsy. On the contrary they differs in various ways from late-onset epileptics with atrophy of known origin and from epileptics with focal lesions.
