Management of epilepsy associated with tuberous sclerosis complex: Updated clinical recommendations

Patients with tuberous sclerosis complex (TSC) are at very high risk for developing epilepsy, and the majority experience seizure onset during the first year of life. Early targeted interventions increase the probability of seizure-freedom and may protect neurodevelopment. In 2012, clinical recommendations for the management of epilepsy in patients with TSC were published by a panel of European experts. Since that time novel studies, reports, and expert opinions in preclinical and clinical TSC-related sciences prompted the need for updated recommendations, including epileptogenesis in TSC, the potential role of predictive biomarkers, the possible benefits of presymptomatic diagnosis and preventive treatment, and new treatment options including mTOR inhibitors. A reconvened panel reviewed the current literature to answer specific questions and five panelists discussed the findings, followed by a general discussion during which all issues were debated to achieve consensus regarding recommendations. A draft manuscript based on these discussions and recommendations was then circulated several times among the panelists, who added their own comments. All the panelists/authors agreed with the final manuscript, which was then submitted for publication. The panel concluded that the need for early diagnosis of TSC-associated seizures is now established, electroencephalographic monitoring has good predictive value for epilepsy before seizure onset in TSC, and, until conclusive data from the EPISTOP trial are available, administration of vigabatrin may be considered in children with subclinical epileptiform EEG discharges. The panel also supported the role of adjunctive everolimus for TSC-associated drug-refractory seizures and emphasized the necessity of early surgical evaluation.