R E V I E W Treatment of Lennox-Gastaut syndrome: overview and recent f indings Kenou van Rijckevorsel Reference Centre of Refractory Epilepsy, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium Correspondence: Kenou van Rijckevorsel Reference Centre for Refractory Epilepsy, Cliniques Universitaires St Luc,Avenue Hippocrate, 10, B-1200 Brussels, Belgium Tel +32 2 7643308 Fax +32 2 7642142 Email vanrijckevorsel@nops.ucl.ac.be Abstract: Lennox-Gastaut syndrome (LGS) is a rare, age-related syndrome, characterized by multiple seizure types, a speciﬁc electro-encephalographic pattern, and mental regression. However, published data on the etiology, evolution, and therapeutic approach of LGS are contradictory, partly because the precise deﬁnition of LGS used in the literature varies. In the most recent classiﬁcation, LGS belongs to the epileptic encephalopathies and is highly refractory to all antiepileptic drugs. Numerous treatments, medical and non-medical, have been proposed and results mostly from open studies or case series have been published. Sometimes, patients with LGS are included in a more global group of patients with refractory epilepsy. Only 6 randomized double-blind controlled trials of medical treatments, which included patients with LGS, have been published. Overall, treatment is rarely effective and the ﬁnal prognosis remains poor in spite of new therapeutic strategies. Co-morbidities need speciﬁc treatment. This paper summarizes the deﬁnition, diagnosis and therapeutic approach to LGS, including not only recognized antiepileptic drugs, but also “off label” medications, immune therapy, diet, surgery and some perspectives for the future. Keywords: Lennox-Gastaut syndrome, treatment, VNS, surgery, epileptic encephalopathies, LGS, refractory Introduction The term Lennox-Gastaut syndrome (LGS) appeared in the literature for the ﬁrst time in 1969 (Niedermeyer 1969), but this syndrome was actually ﬁrst described by Lennox and Davis in 1950 and by Gastaut et al in 1966. The International League Against Epilepsy (ILAE) Commission (Classiﬁcation Epilepsia 1989) classiﬁed LGS among the cryptogenic or symptomatic generalized epilepsies, but, more recently, the ILAE Task Force classiﬁed it among the age-related epileptic encephalopathies (Engel 2001). LGS comprises atypical absences with slow spike-and-wave (SW) complexes, tonic seizures that are mostly sleep-related, and cognitive deterioration (ILAE). However, LGS has also been deﬁned as diffuse SW pattern on electroencephalogram (EEG), mental retardation, and multiple types of seizures without reference to age or to nocturnal tonic seizures (French et al 2004). This broader deﬁnition, mostly used in the US, may include for example, Dravet syndrome, Doose syndrome, or focal cryptogenic epilepsies, especially of frontal lobe origin. According to Genton et al (2000), EEG criteria should include not only bilateral slow SW but also 10–20 Hz epileptic fast rhythms, predominantly in sleep. Furthermore, this syndrome belongs to the age-related epileptic encephalopathies and starts during childhood. When using these full criteria, LGS appears to be rare. Largely as a result of the different deﬁnitions, the literature presents, or seems to present, contradictory data about the frequency of seizure types, epidemiology, treatment options, prognosis, and long term evolution of LGS. Furthermore, results of clinical studies are difﬁcult to compare in terms of efﬁcacy and most of them, especially randomized studies, do not cover more than a few weeks (Hancock and Cross 2003). Neuropsychiatric Disease and Treatment 2008:4(6) 1001–1019 © 2008 Dove Medical Press Limited. All rights reserved 1001