Update on Drug Management of Refractory Epilepsy in Tuberous Sclerosis Complex

Paediatr Drugs. 2020 Feb;22(1):73-84. doi: 10.1007/s40272-019-00376-0.


Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder with epilepsy as a common and early presenting symptom. The neurological phenotype, however, is variable and unpredictable. Early and refractory seizures, infantile spasms in particular, are associated with a poor neurological outcome. Preliminary data suggests early and aggressive seizure control may mitigate the detrimental neurodevelopmental effects of epilepsy. For infantile spasms, vigabatrin is the first line of treatment, and steroids and classic antiepileptic drugs (AEDs) are suitable for second line. Based on retrospective data, vigabatrin should be considered for other indications, especially in infants with focal seizures, as this may prevent infantile spasms, but also in children and adults with epileptic spasms and tonic seizures. Otherwise, for most seizure types, treatment is similar to that for patients without TSC, including the use of novel AEDs, although limited data are available. Three major developments are changing the field of epilepsy management in TSC. First, final recommendations on preventive treatment with vigabatrin will result from two multicenter trials in the US (PREVeNT, clinicaltrials.gov #NCT02849457) and Europe (EPISTOP, clinicaltrials.gov #NCT02098759). Second, treatment with everolimus, an inhibitor of the mechanistic target of rapamycin (mTOR), reduced seizures when compared to placebo. Further, mTOR inhibitors may have an overall disease-modifying effect. Third, the role of cannabidiol in the treatment of refractory seizures in TSC is yet to be established. With treatment recommendations in TSC, we keep an eye on the prize for the broader field of pediatric epilepsy: the lessons learned from TSC are likely applicable to other epileptic encephalopathies.

Publication types

  • Review

MeSH terms

  • Adult
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Drug Resistant Epilepsy / drug therapy*
  • Female
  • Humans
  • Male
  • Retrospective Studies
  • Tuberous Sclerosis / complications
  • Tuberous Sclerosis / drug therapy*
  • Young Adult


  • Anticonvulsants

Associated data

  • ClinicalTrials.gov/NCT02849457
  • ClinicalTrials.gov/NCT02098759