van Rijckevorsel therapeutic role of gene therapy in epilepsy and to evaluate safety concerns and possible side-effects. Conclusions The ultimate goal of epilepsy treatment is to achieve seizure control in a safe manner. Seizure freedom appears to be unrealistic in some refractory epilepsies, especially LGS. Four AEDs (FBM, LTG, TPM and RUF) have been ofﬁcially licensed for LGS after demonstrating signiﬁcant efﬁcacy in randomized, double-blind, placebo controlled studies. Older AEDs (especially VPA) are regularly used, based on more than 40 years of clinical practice. Published results, even from randomized studies, are difﬁcult to compare. Each trial looked at different patient populations, with diverse co-medications and etiologies, and considered different outcomes for efﬁcacy. Unfortunately, a “magic pill” does not exist, and for that reason, other treatments are regularly tried. For children with highly pharmacoresistant seizures, an individual and tailored treatment strategy is necessary (Figure 1), based on the likelihood of better seizure control and QOL balanced against the likely risks for each strategy (diet, stimulation, surgery, etc). It is reasonable to consider non-medical treatments after failure of two to three AEDs. The different steps of this con- tinuous therapeutic approach should depend on various factors, including patient characteristics, severity of seizures and mental handicap, and local availability of sophisticated techniques. Psychiatric problems or severe mental handicap are no longer considered as contra-indications for surgery. Multiple seizure types in a child with mental stagnation/regression Confirmation of LGS, research of etiologic factors Add-on of Topiramate or Rufinamide or Lamotrigine Valproate Felbamate Presurgical evaluation Focal or regional lesions No lesion Surgery: resection, disconnection, multiple subpial transections, etc. VNS Ketogenic diet Callosotomy Figure 1 Treatment strategy for children with highly pharmacoresistant seizures. 1014 Several subsequent medication trials with a maximum of 3 chronic antiepileptic drugs Off-label or in development antiepileptic drugs Neuropsychiatric Disease and Treatment 2008:4(6)