title: Long-term effect of everolimus on epilepsy and growth in children under 3 years of age treated for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.
abstract: BACKGROUND
  Tuberous sclerosis complex (TSC) is a genetic disorder characterized by increased mammalian target of rapamycin (mTOR) activation and growth of benign tumors in several organs throughout the body. In young children with TSC, drug-resistant epilepsy and subependymal giant cell astrocytomas (SEGAs) present the most common causes of mortality and morbidity. There are also some reports on the antiepileptic and antiepileptogenic potential of mTOR inhibitors in TSC. However, the data on everolimus efficacy and safety in young children are very limited.
  
  
  OBJECTIVE
  To show the long-term safety data and the effect of everolimus treatment on epilepsy in children under the age of 3 who received everolimus for SEGAs associated with TSC.
  
  
  METHODS
  We present the results of everolimus treatment in 8 children under the age of 3 who participated in EXIST-1 study. Five patients presented with active, drug-resistant epilepsy at baseline. The mean follow-up is 35 months (33-38 months) and all children are still on treatment.
  
  
  RESULTS
  In 6 out of 8 children, at least a 50% reduction in SEGA volume was observed. In 1 child with drug-resistant epilepsy, everolimus treatment resulted in cessation of seizures and in 2 other children, at least a 50% reduction in the number of seizures was noted. The incidence of adverse events (AE) was similar to that observed in older children and adults.
  
  
  CONCLUSIONS
  This study suggests that everolimus is effective and safe in infants and young children with epilepsy and SEGA associated with TSC and offers a valuable treatment option.
authors.affiliation: Department of Science, The Children's Memorial Health Institute, Warsaw, Poland. k.kotulska@czd.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kotulska
authors.forename: Dariusz
authors.initials: D
authors.lastname: Chmielewski
authors.forename: Julita
authors.initials: J
authors.lastname: Borkowska
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Jurkiewicz
authors.forename: Dariusz
authors.initials: D
authors.lastname: Kuczyński
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kmieć
authors.forename: Barbara
authors.initials: B
authors.lastname: Łojszczyk
authors.forename: Dorota
authors.initials: D
authors.lastname: Dunin-Wąsowicz
authors.forename: Sergiusz
authors.initials: S
authors.lastname: Jóźwiak
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D001254:Astrocytoma / Q000150:complications / Q000188:drug therapy*; D002675:Child, Preschool; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy*; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects; D013995:Time; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000927:Anticonvulsants; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Adverse events; Epilepsy; Everolimus; SEGA; Safety; TSC; Young children