Review 10.1517/14656560802618647 © 2009 Informa UK Ltd ISSN 1465-6566 5 All rights reserved: reproduction in whole or in part not permitted Pharmacotherapy of idiopathic generalized epilepsies Paolo Curatolo † , Romina Moavero, Adriana Lo Castro & Caterina Cerminara Tor Vergata University, Pediatric Neurology Unit, Department of Neurosciences, Rome, 00133, Italy Background : Idiopathic generalized epilepsies (IGE) represent about 20% of all epilepsies, are genetically determined and comprise several subgroups of syn- dromes. Although complete seizure control is achievable in about 80% of patients with IGE syndromes, a substantial group remains with inadequate control and unsatisfactory long-term outcome. Several new antiepileptic drugs (AEDs) have been studied in children with IGE. Objectives and Methods : To review the rational drug choice for these patients, the PubMed database was searched with the keywords IGE and AEDs. Results : Older AEDs continue to play a major role in the treatment of IGE. Although the first line monotherapy is still with sodium valproate, new drugs like lamotrigine, levetiracetam and topiramate, are increasingly used in the treatment of IGE. Conclusions : Further research on evidence-based treatment of IGE with new AEDs is needed. New data from molecular genetics of IGE might have the potential to help clinicians choose the most appropriate antiepileptic therapy. Keywords: antiepileptic drugs, idiopathic generalized epilepsy , lamotrigine, levetiracetam, valproate Expert Opin. Pharmacother. (2009) 10(1):5-17 1. Introduction Idiopathic generalized epilepsies (IGE) are a category of disorders defined by strict clinical and EEG features proposed by the International League Against Epilepsy (ILAE) classification of epileptic syndromes [1-3]. The prevalence of IGE has been assessed to be about 20% of all epilepsies [4]. They are genetically determined, affecting otherwise normal people, and manifest with absence seizures, myoclonic seizures or generalized tonic-clonic seizures (GTCS). The interictal EEG shows generalized spike-polyspike and slow-wave discharges, which are often precipitated by hyperventilation and sleep deprivation. IGE are usually easy to diagnose when clinical and EEG data are properly collected. Syndromic diagnosis may not be apparent at first presentation, and close clinical and EEG follow-up is often necessary to complete the final diagnosis [5]. Most syndromes of IGE are lifelong disorders [6]; long-term social outcome could be unsatisfactory even if epilepsy remits, and some patients have behavioural or learning difficulties [7]. IGE comprise of several subgroups of syndromes, including: childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), epilepsy with myoclonic absence (EMA), juvenile myoclonic epilepsy (JME), epilepsy with GTCS, myoclonic astatic epilepsy (MAE or Doose syndrome), and generalized epilepsy with febrile seizures plus (GEFS+). Syndrome diagnosis could be helpful in guiding investigations and management, and is an early prognostic indicator. However, based on clinical experience, it is sometimes difficult to identify the boundaries of the syndromes. As a result of the overlapping features between different IGE, the term IGE with variable phenotypes has been suggested as all-inclusive [2]. Several studies of twins and families have shown that genetic factors play a strong role in the aetiology of IGE [8,9]. There is higher concordance for IGE in monozygotic than dyzigotic twins (0.76 vs 0.33) [9]. IGE usually have complex inheritance [10] associated with the interaction of two or more genes; only a small 1. Introduction 2. Seizures of idiopathic generalized epilepsies 3. Syndromes of idiopathic generalized epilepsies 4. Treatment 5. Expert opinion Expert Opin. Pharmacother. Downloaded from informahealthcare.com by Univ Napoli on 06/03/10 For personal use only.