[Antiepileptic drugs]. / Farmacos antiepilepticos.

We report the most notable pharmacokinetic and pharmacodynamic characteristics of the antiepileptic drugs commercialised in the last four years (eslicarbazepine acetate, brivaracetam and perampanel). Their efficacy and safety are analysed in open-label clinical trials, which are the ones that reproduce their use in everyday life, without the rigid protocols used in clinical trials.

TITLE: Farmacos antiepilepticos.Se refieren las caracteristicas farmacocineticas y farmacodinamicas mas destacadas de los farmacos antiepilepticos comercializados en los cuatro ultimos años (acetato de eslicarbacepina, brivaracetam y perampanel). Se analiza su eficacia y tolerabilidad en estudios clinicos abiertos, que son los que reproducen su utilizacion en la vida diaria, sin los protocolos rigidos de los ensayos clinicos.

[Rufinamide. A review of its pharmacokinetic and pharmacodynamic properties]. / Rufinamida. Revisión de sus propiedadesfarmacocinéticas y farmacodinámicas.

AIM: To review the most important research published on the pharmacokinetic and pharmacodynamic properties of rufinamide (RFM), together with the outcomes of the clinical trials conducted to date with this new antiepileptic drug. DEVELOPMENT: RFM is a triazole derivative with no structural relation to the other antiepileptic drugs, and the effectiveness and safety profiles shown in laboratory animals suggest that it could be effective in the treatment of partial and generalised seizures. In fact, in double-blind trials RFM has proved to be effective and well tolerated in adults with intractable partial seizures and in patients between 4 and 30 years of age with Lennox-Gastaut syndrome. CONCLUSIONS: Based on the results of clinical trials, RFM has been approved in the European Union for specific use in patients with Lennox-Gastaut syndrome and therefore represents a new therapeutic alternative with which to offset the medication resistance of this epileptic encephalopathy.

[Rational combination therapy in epilepsy. III. Possible associations between antiepileptic drugs]. / Politerapia racional en epilepsia. III. Posibles asociaciones de antiepilépticos.

INTRODUCTION: As the foundation underlying rational combination therapy it is necessary to consider the mechanism of action of each antiepileptic drug, its spectrum, the safety and pharmacodynamic and pharmacokinetic interactions, and to select the association of antiepileptic drugs in accordance with these factors. DEVELOPMENT: This paper consists of three parts. In this third part we consider possible associations between antiepileptic drugs; we suggest associations that may be beneficial, others that must be kept under surveillance because their advantages can be offset by their drawbacks, and others that should be avoided because their disadvantages outweigh their possible advantages. CONCLUSIONS: Until more is known about the aetiopathogenesis of epilepsy and we have markers of the cause of epilepsy in a particular patient it will not be possible to associate antiepileptic drugs according to their mechanisms of action. The absence of clinical trials only allows us to make suggestions about possible beneficial or harmful associations depending on the pharmacodynamic and pharmacokinetic characteristics of antiepileptic drugs, which can thus enhance their effectiveness and safety.

[Rational combination therapy in epilepsy. II. Clinical and pharmacological aspects]. / Politerapia racional en epilepsia. II. Aspectos clínicos y farmacológicos.

INTRODUCTION: From an analysis of the studies published to date, the criteria used to select the antiepileptic drugs that can be associated for the treatment of a particular situation or patient need to be optimised because combination therapy offers a low level of evidence. It is also acknowledged that it is advisable to begin treatment with monotherapy (although 30% of patients do not respond and in such cases combination therapy is usually employed), but the possibility of starting with bitherapy in epilepsies that are usually resistant to treatment has also been suggested. DEVELOPMENT: This paper consists of three parts. This second part reviews the foundations underlying the rational association of antiepileptic drugs. CONCLUSIONS: For the association of antiepileptic drugs to result in increased effectiveness without raising the level of toxicity, the theoretical bases of rational combination therapy take into account the mechanism of action, the spectrum, the safety, and the pharmacodynamic and pharmacokinetic interactions of each antiepileptic drug; the number of times the drug is taken is another factor to be taken into consideration. Although it is still early to associate two antiepileptic drugs on the basis of their mechanism of action, these theoretical foundations suggest a sodium channel inhibitor should be associated with a GABAergic agent or an antiepileptic with multiple mechanisms and that we should avoid the association between antiepileptic drugs with additional (sedative and neurological) toxicity or that are likely to interact. Evaluation of the effectiveness, safety, interactions and number of doses suggests the following order, from more to less suitable for combination therapy: levetiracetam/pregabalin > gabapentin > lamotrigine > oxcarbazepine/topiramate/zonisamide > tiagabine > valproic acid > carbamazepine > phenytoin > phenobarbital/primidone > benzodiazepines.

[Rational combination therapy in epilepsy. I. Concepts and foundations]. / Politerapia racional en epilepsia. I. Concepto y fundamentos.

INTRODUCTION: It is an accepted fact that it is wise to start antiepileptic treatment with monotherapy, but 30% of patients do not respond to it or to several monotherapies; in that moment an association of two or more antiepileptic drugs is commonly utilised (the appearance of ten second-generation antiepileptic drugs on the market has not changed this scenario to any significant extent). Yet, on the other hand, the use of bitherapy in epilepsies that are usually resistant to treatment has been suggested as a interesting way to begin treatment. DEVELOPMENT: This article consists of three parts. In this first part we review the concept of rational combination therapy, the concept of how and when it should be used and the studies about associations of antiepileptic drugs conducted in animals and in humans. CONCLUSIONS: Although combination therapy is frequent as treatment for epilepsy, it is not always so obvious that it offers more benefits in terms of greater effectiveness with a lower, or at least equal, degree of toxicity. Few methodologically correct clinical trials have been conducted and recent reviews continue to consider that no controlled clinical trials have been carried out that confirm the benefits of combination therapy. This does not mean, however, that rational combination therapy is totally void of any kind of usefulness, but rather it stresses the fact that it offers a low level of evidence.

[Cognitive repercussion of early-onset epilepsies]. / Repercusión cognitiva de las epilepsias precoces.

INTRODUCTION: From time to time the debate over whether early-onset epileptic seizures are harmless or have harmful effects on the developing brain reappears. DEVELOPMENT: We evaluated the results of clinical studies reporting the long-term cognitive development of children who suffer from early-onset epilepsies, that is to say, in children with brain immaturity: neonatal epilepsies, West's syndrome, Dravet's syndrome, benign myoclonic epilepsy in infancy, myoclonic-astatic epilepsy and Lennox-Gastaut syndrome; we also report on the harmful influence of certain antiepileptic drugs, such as phenobarbital and valproate, on the immature brain. CONCLUSIONS: The negative repercussion of early-onset epilepsies on the immature brain is unquestionable, with sometimes very intense impairment of cognitive development. As a result, we make the following recommendations: early electro-clinical diagnosis, immediate treatment, timely change of medication if the seizures persist, avoid phenobarbital and valproate, and try other drugs or compounds that have proved to have neuroprotective effects in experimental studies.

[Hypothalamic hamartoma: clinical characteristics. Electroencephalogram and brain magnetic resonance imaging in 10 patients]. / Hamartomas hipotalámicos: características clínicas, electroencefalograma y resonancia magnética cerebral en 10 pacientes.

INTRODUCTION: We describe clinical findings and electroencephalogram (EEG) in patients with hypothalamic hamartoma and epilepsy. METHODS: Our group includes 10 patients (eight males) with mean age of 17.8 years (range: 7-39) and hypothalamic hamartoma in the brain magnetic resonance imaging (MRI). We analyzed clinical data, seizure semiology, MRI and EEG findings of the neuropsychological study. RESULTS: Nine patients had gelastic seizures, that initiated at a mean age of 17.1 months (2 days-5 years). Other types of seizure were observed in seven and five had behavior disorders. Intelligence quotient (IQ) was below the mean range in three. Three children had precocious puberty and thyroid dysfunction. One patient did not have epilepsy. MRI showed a hypothalamic lesion suggesting hamartoma associated to a dysplastic lesion in one case. The interictal EEG was normal in 2 cases and revealed epileptiform abnormalities, consisting of spikes or sharp waves, in temporal regions, frontal, fronto-temporal regions and central-parietal in 8. Three patients had paroxysmal discharges of generalized fast activity (> 10 Hz) during non-REM sleep. Forty seizures were recorded, 31 had an ictal EEG pattern while the EEG was normal in 9. CONCLUSIONS: In our group gelastic seizures were an early and constant finding except in one patient. Partial complex seizures, behavior alteration and cognitive decline were frequent. Video-EEG monitoring allows us to identify interictal and ictal patterns that have been described in hypothalamic hamartomas.

[Pharmacogenetics, pharmacogenomics and individualised antiepileptic therapy]. / Farmacogenética, farmacogenómica y terapia antiepiléptica individualizada.

AIMS: Despite the large number of antiepileptic drugs (AED) currently on the market, in 20-30% of patients it is still not possible to achieve a total control of the seizures or to prevent the appearance of idiosyncratic side effects. DEVELOPMENT: In this study the pharmacokinetic and pharmacodynamic factors involved in pharmacoresistance in epilepsies are analysed, with special attention given to the polymorphisms of metabolising enzymes or their inducers, particularly the hepatic cytochrome CYP, the over-expression of membrane-transporting proteins -P-glycoprotein (PGP), MRP- and polymorphisms in the ion channels. Idiosyncratic effects are produced due to an imbalance between the production of toxic metabolites and the individual capacity to detoxify them. Pharmacogenetics and pharmacogenomics can identify certain personal, biochemical, enzymatic and genetic characteristics that are of use in selecting the most effective AED with the lowest risk of idiosyncratic effects for each person. CONCLUSIONS: Although new AED that can help reduce the number of medication resistant patients must be introduced, at the same other therapeutic strategies have to be developed with the aid of pharmacogenomics; more specifically there is a need for AED that are not transported by PGP o MRP, or substances that antagonise those membrane transporters and make it possible for the AED to reach the site where they are to act. Furthermore, the detoxification capacity of each individual must be known in order to be able to minimise the risk of idiosyncratic side effects.

[Effectiveness and safety of levetiracetam in 133 children with medication resistant epileptic seizures]. / Eficacia y tolerabilidad del levetiracetam en 133 niños con crisis epilépticas farmacorresistentes.

INTRODUCTION: Levetiracetam (LEV) is the latest drug approved in the European Union for use in polytherapy in children over 4 years of age with partial epileptic seizures that are resistant to other antiepileptic drugs. AIM. To report our experience of associating LEV in children with medication resistant epileptic seizures. PATIENTS AND METHODS: We conducted an open, observational, respective study involving 133 children with refractory epilepsies: 106 with focal seizures and 27 with other types of seizures. LEV was associated over a period of more than 6 months and we evaluated its repercussion on the frequency of the seizures and the side effects related to the drug. RESULTS: With average doses of LEV of 1,192 +/- 749 mg/day the frequency of the seizures was reduced by over 50% in 58.6% of cases and seizures were quelled in 15.8% of patients. Side effects were produced in 27.8% of cases, and were usually transient or tolerable; these effects led to withdrawal of LEV in only eight cases (6.02%). In 37 children (27.8%), their relatives noted an improvement in their social behaviour and cognitive abilities. CONCLUSIONS: a) LEV is an effective drug that is well tolerated in children with refractory epilepsy; b) Its effectiveness in different types of seizures indicates a broad therapeutic spectrum; and c) LEV can even condition favourable secondary effects, a circumstance that has been reported only exceptionally in the case of other antiepileptic drugs.

[The clinical and economic impact of generic drugs in the treatment of epilepsy]. / Impacto clínico y económico de los fármacos genéricos en el tratamiento de la epilepsia.

AIMS: The aim of this study was to determine whether the introduction of generic formulations of antiepileptic drugs (AED) would lead to an economic saving for the public health service. DEVELOPMENT: The narrow therapeutic index, low solubility and non-linear pharmacokinetics of some AED mean that the ranges of bioequivalence that are authorised for generic formulations do not offer the same results regarding effectiveness and safety as those obtained by brand name drugs. This is why the potential saving stemming from the use of generic AED may be exceeded by the costs deriving from the consequences conditioned by their utilisation. These are the conclusions that can be drawn from the results of cost and effectiveness analyses conducted on two hypothetical cases of substituting (9 and 20%) treatments involving brand name carbamazepine (CBZ) with generic formulations. If a generic CBZ were introduced into the treatment of 9% of the patients taking this drug, the annual cost for one person with epilepsy would rise by 38.17 as compared to treating all these patients with brand name CBZ (marginal cost-effectiveness), and overall spending on health care in the country would grow by 2,748,000 (cost-benefit analysis). These figures rise sharply when 20% of treatments with brand name CBZ are replaced by generic formulations. CONCLUSIONS: The bioequivalence ranges authorised for generic formulations may be inappropriate for generic AED. With certain AED, replacing a brand name product with a generic version of the same medication can have negative effects on the amount of health care resources that are consumed and, therefore, on the overall economic expenditure associated with epilepsy.

[Oxcarbazepine in monotherapy in 324 patients with partial seizures (TRINOVA study)]. / Oxcarbacepina en monoterapia en 324 pacientes con crisis parciales (estudio TRINOVA).

AIMS: The purpose of this study was to evaluate the effectiveness and tolerability of oxcarbazepine (OXC) administered as monotherapy in patients with partial seizures as a first therapeutic alternative or after the failure of other monotherapies. PATIENTS AND METHODS: A prospective, open, multicentre trial based on observation involving 324 patients between 6 and 87 years of age with partial seizures who had not received prior treatment with antiepileptic drugs (AED) (n = 114) or in whom other monotherapies had failed (n = 210). These patients were administered OXC in the conditions usually found in clinical practice over a period of 52 weeks; effectiveness was evaluated by the reduction in the frequency of the seizures, tolerability was measured through the side effects related to the drug and quality of life was assessed by means of the changes reflected in the CAVE questionnaires, in the case of children, and the QOLIE-31 for adults. RESULTS: At the end of the study, total control over the seizures was 73.7% in patients who had not been treated previously and 43.8% in those in whom other monotherapies had failed; at the same time there was an improvement in the quality of life parameters. 42.9% reported side effects, which were usually tolerable or transient since they led to the withdrawal of OXC in only 9.6% of the patients. CONCLUSIONS: OXC is a very effective AED and is well tolerated as monotherapy in patients of all ages with partial seizures, either as the first choice therapy or as a substitution for other ineffective or poorly tolerated drugs.

[Intranasal and buccal midazolam in the treatment of acute seizures]. / Midazolam intranasal y bucal en el tratamiento de las convulsiones agudas.

AIMS: There are several personal and social problems involved in the administration of rectal diazepam that make it unsuitable for use in public places and by non medical workers, in children and especially in teenagers and adults. Intranasal and oral midazolam could be an alternative to rectal diazepam. We review the efficacy and safety of these ways of administering midazolam, which is already used in some countries as a sedative and as an anticonvulsive drug, despite the fact that it has not yet received authorisation. DEVELOPMENT: Intranasal midazolam (INM) was first used as a sedative in dental extractions, echocardiography, endoscopies or surgery, especially in children. After proving its efficacy electroencephalographically in patients with seizures, it started to be used to interrupt acute seizures. In three randomised trials, the efficacy of intranasal and oral midazolam in hospitalised patients was similar to, and even higher than, that of intravenous or rectal diazepam, with a similar speed of action and safety; no studies have been conducted, however, in the extra hospital milieu and its risk of respiratory depression may be like that of other benzodiazepines. One of the problems of using the parenteral solution for intranasal administration is the irritation that is produced by its acidic pH and the relatively large volume that has to be administered. These problems could be reduced by using aerosols containing a solution of midazolam in cyclodextrin, which accomplishes a greater concentration with a pH that is less acidic. Oral administration can be used in patients with nasal secretions or intense movements of the head. CONCLUSIONS: Intranasal or oral midazolam can improve the treatment of acute seizures in the hospital milieu and, more especially, in the extra hospital milieu when patients are attended by non medical staff. There is a need, however, for trials that prove its efficacy and safety in this situation.

[Pharmacology in epilepsy. Where are we heading for?]. / Farmacología en epilepsia. Hacia dónde vamos?

AIMS: The aim of this study was to conduct a critical evaluation of the contribution made by the latest antiepileptic drugs (AED) and to describe the pharmacological therapeutic strategies, which do not contemplate the use of traditional AED, employed to treat pharmacoresistant patients. DEVELOPMENT: After comparing the mechanisms of action, as well as the pharmacokinetic and pharmacodynamic characteristics of the classical and new AED, and examining the advantages and disadvantages of each of them, it still turns out to be impossible to achieve a total control of seizures in 20-25% of cases. This is due to the polymorphisms of the enzymes and of their inducers, to the over-expression of the carrier proteins (PGP, MRP) and to polymorphisms undergone by the receptors. CONCLUSIONS: Although there is a need for new AED to be synthesized which can be used to attempt to reduce the rate of pharmacoresistant patients, other strategies must also be developed in the field of pharmacogenomics, and more specifically with regard to AED that are not carried by PGP or MRP. Another important area is that of substances that antagonize these carriers and, thus, allow AED to reach the site where they are to act.

[Effectiveness and tolerability of levetiracetam in 43 children and adolescents with epilepsy]. / Eficacia y tolerabilidad del levetiracetam en 43 niños y adolescentes con epilepsia.

INTRODUCTION: Levetiracetam (LEV) is the latest antiepileptic drug (AED) to be marketed, and is indicated for use in association in adults with focal seizures. AIMS: The purpose of this study is to report on our experience of administering LEV to children and adolescents with pharmacoresistant epilepsies. PATIENTS AND METHODS: Retrospective open trial involving the observation of 43 children and adolescents with refractory epilepsies, using associated LEV for more than 6 months on an individual basis, the aim of which was to evaluate the repercussions on the frequency of the seizures, together with the adverse and beneficial side effects of LEV administration. RESULTS: With mean doses of LEV of 45.01 +/- 33.02 mg/kg/day the frequency of seizures was reduced by >50% in 65% of patients, while seizures were completely eradicated in 14% of patients; adverse side effects were reported in 28% of patients, although these were usually transient or tolerable, as LEV administration only had to be stopped for this reason in two cases (4.65%). Relatives noted an improvement in social behaviour and in cognitive skills in the case of 15 children (34.9%). CONCLUSIONS: 1. LEV is an effective drug that is well tolerated in children and adolescents with refractory epilepsies; 2. Its effectiveness in different types of seizures suggests a broad therapeutic spectrum; 3. LEV is a well tolerated drug with favourable side effects, a fact that is rarely reported with regard to other AED.

[Levetiracetam in children and adolescents with epilepsy]. / Levetiracetam en niños y adolescentes con epilepsia.

AIMS: The aim of this paper is to report on the clinical experiences that have been published concerning the association of levetiracetam (LEV) in children and adolescents with refractory epilepsies. DEVELOPMENT: Although LEV has been approved for use in polytherapy in patients over the age of 16, some short works (communications and posters in international congresses) and three open studies have already dealt largely with the fact that the drug has been associated in children and in adolescents under the age of 16, with all types of refractory seizures, especially focal seizures. Half the patients can be considered to be responders, since the seizure rate is reduced by more than 50% when LEV is associated, and were completely eradicated in 16% of cases. In a third of the cases side effects were reported, although they can be seen as being mild and transient since they meant that LEV application was interrupted in less than 10% of cases. CONCLUSIONS: LEV is a drug that is effective and well tolerated in children and adolescents with difficult-to-treat epilepsies; it is very straightforward to manage due to its excellent pharmacokinetic characteristics and suggested dosages at these ages are between 40 and 50 mg/kg/day (up to 3,000 mg per day, in two doses).

[Severe myoclonic epilepsy in infancy (Dravet's syndrome). Some genetic aspects]. / Epilepsia mioclónica grave de la infancia (síndrome de Dravet). Aspectos genéticos.

AIMS: The purpose of this study is to survey the data from the literature on the subject of the possible genetic origin of severe myoclonic epilepsy in infancy (SMEI). DEVELOPMENT: SMEI must inevitably be included within the phenotype of febrile seizures, which is made up of febrile seizures, febrile seizures plus, generalized epilepsy with febrile seizures plus, myoclonic astatic epilepsy and SMEI itself. We describe the five gene loci localized in children with febrile seizures (FEB 1 5), the three genes identified in patients with generalized epilepsy with febrile seizures plus (GEFS+ 1 3) and the de novo mutations of gene SCN1A that have been identified to date in children with SMEI. CONCLUSIONS: SMEI, the severest form of the phenotypic spectrum of febrile seizures plus, is a channelopathy that is produced de novo, that is, during meiosis. Its prognosis may be conditioned by the kinds of mutations it is due to, and which are very different to those that induce other, more benign epileptic syndromes from the same phenotypic spectrum.

[Gabapentin: its mechanisms of action in the year 2003]. / Gabapentina: mecanismos de accion en el año 2003.

AIMS: The purpose of our study was to survey the data from the main research work published about the mechanisms of action of gabapentin. DEVELOPMENT: In addition to an unquestionable Gabaergic effect, gabapentin is the first antiepileptic that has been shown to have an effect on the a2d subunit of the voltage dependent calcium channels and on hyperpolarization activated cationic (Ih) currents. Gabapentin also exerts an indirect effect on the voltage dependent sodium channels, slightly inhibits glutamate and reduces the excretion of certain neurotransmitters, such as serotonin, dopamine and noradrenalin. CONCLUSIONS: Gabapentin has a number of original mechanisms of action with which to account for its effects in epilepsies and in many other clinical entities.

[Advances in physiopathology and the treatment of neuropathic pain]. / Avances en la fisiopatología y en el tratamiento del dolor neuropático.

AIMS: In this paper we review the most significant studies on the treatment of neuropathic pain over the last few decades, as well as the most recent research work in which the physiopathological mechanisms of pain, with the intention of looking for evidence based criteria that can help us to choose the most appropriate treatment. METHOD: The physiopathological bases of neuropathic pain are founded, peripherally, on alterations in the neuronal excitability mediated by voltage dependent sodium channels; from the central point of view, the chief neurotransmitter involved is glutamate, which allows calcium to enter through the N-methyl D-aspartate receptor and conditions a more prolonged depolarisation and the activation of secondary messengers. This determines the chronification of the pain. Thanks to these physiopathological findings about pain, some of the new antiepileptics, which inhibit the sodium channels or the calcium channels, increase the GABA or reduce the level of glutamate in the synapses, have been added to the already existing classic forms of medication. CONCLUSIONS: Different neurophysical alterations induce the most diverse clinical manifestations, such as paresthesia, hyperalgesia or allodynia, regardless of the etiological processes that condition them. The efficiency of tricyclic antidepressants and of carbamazepine is made clear in different clinical studies, but the new antiepileptics (with the exception of gabapentin) have frequently been used in open clinical studies, which means there is a need for double blind controlled clinical trials in order to determine the efficiency and the tolerability of the different therapeutic alternatives in each of the clinical manifestations of neuropathic pain.

[Characteristics and indications of oxcarbazepine]. / Características e indicaciones de la oxcarbacepina.

OBJECTIVE: To review the major studies published concerning the pharmacokinetic characteristics, mechanism of action, clinical efficacy and adverse effects of oxcarbazepine (OXC). DEVELOPMENT: OXC is a ketoderivative of carbamazepine (CBZ), with a similar mechanism of action, possibly widening the voltage dependent potassium channels. Its pharmacokinetic characteristics are much better than those CBZ but the frequency and intensity of interactions is much less. In several double blind trials, using the drug in monotherapy in previously untreated patients, similar efficacy was found after OXC, phenytoin, valproate and CBZ but the fewest adverse effects were seen after OXC. CONCLUSIONS: OXC is an antiepileptic drug with better pharmacokinetic properties than CBZ and similar clinical efficacy, but better tolerated, so it may therefore be expected to replace this classical antiepileptic drug for use in monotherapy and polytherapy of both children and adults in all types of partial seizures.

[Characteristics and indications of levetiracetam]. / Características e indicaciones del Levetiracetam.

OBJECTIVE: To describe the data contained in the most important studies published on the pharmacokinetic and pharmacodynamic properties of levetiracetam, and also the main clinical trials carried out using this new antiepileptic drug. DEVELOPMENT: Derived from piracetam, but with very different properties, levetiracetam is ineffective in the usual models of seizures induced in experimental animals, although it acts in models of prolonged activation, audiogenous seizures and absences and has a novel mode of action. It has pharmacokinetic properties which are nearer to that of the ideal anti epileptic drug. In clinical trials done in adults with partial epilepsies use of 1,000 to 4,000 mg of levetiracetam was significantly more effective than a placebo, and the drug was very well tolerated. CONCLUSIONS: Levetiracetam is the newest antiepileptic drug to appear on the market. Its pharmacodynamic and pharmacokinetic characteristics are excellent. It has currently been approved for use in the polytherapy of patients with partial seizures aged over 16 years. Several studies indicate that its therapeutic spectrum is probably wider, particularly in generalized seizures such as the myoclonias, absences and seizures induced by light stimulation. Thus the indications for levetiracetam may become clear over the next few years.