title: Mammalian target of rapamycin inhibitors for intractable epilepsy and subependymal giant cell astrocytomas in tuberous sclerosis complex.
abstract: OBJECTIVE
  To evaluate the efficacy and side effects of oral mammalian target of rapamycin (mTOR) inhibitors in children and adolescents with tuberous sclerosis complex (TSC) and intractable epilepsy or subependymal giant cell astrocytoma (SEGA).
  
  
  METHODS
  Single-center series of 13 children and adolescents with TSC who received sirolimus or everolimus (mTOR inhibitors). The anticonvulsant response was evaluated in 7 patients with TSC and refractory seizures. Six patients with SEGAs were treated with either sirolimus or everolimus for nonsurgical management. SEGA volumes were assessed longitudinally using 1.5-T magnetic resonance imaging.
  
  
  RESULTS
  Of the intractable seizure group (7 patients), 1 patient had >90% reduction, 4 had 50%-90% reduction, and 2 had <50% reduction. Three reported subjective improvements in learning. By 12 months of treatment, there were statistically significant reductions in the SEGA volumes in 4 patients who received mTOR inhibitors (P < .04). The mean SEGA volume after 6 months of treatment was 2.18 cm(3), which represents 33% reduction in the mean baseline volume of 3.26 cm(3). The mTOR inhibitors were well tolerated. Adverse effects include dyslipidaemia (3 of 13), gingivitis (1 of 13), anorexia (1 of 13), and mild gastrointestinal side effects (1 of 13).
  
  
  CONCLUSIONS
  This case series suggests that mTOR inhibitors can improve seizures in those with TSC and refractory epilepsy. They are also an effective treatment for reducing the volume of SEGAs in patients with TSC not amenable to surgery with an acceptable side effect profile.
authors: Department of Neurology, Sydney Children's Hospital, Randwick, New South Wales, Australia; The School of Women's and Children's Health, Medicine UNSW, University of New South Wales, Sydney, New South Wales, Australia. Electronic address: mcardamone@yahoo.com.
authors: Michael
authors: M
authors: Cardamone
authors: Department of Neurology, Sydney Children's Hospital, Randwick, New South Wales, Australia; The School of Women's and Children's Health, Medicine UNSW, University of New South Wales, Sydney, New South Wales, Australia.
authors: Danny
authors: D
authors: Flanagan
authors: Department of Medical Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia; The School of Women's and Children's Health, Medicine UNSW, University of New South Wales, Sydney, New South Wales, Australia.
authors: David
authors: D
authors: Mowat
authors: Department of Nephrology, Sydney Children's Hospital, Randwick, New South Wales, Australia; The School of Women's and Children's Health, Medicine UNSW, University of New South Wales, Sydney, New South Wales, Australia.
authors: Sean E
authors: SE
authors: Kennedy
authors: Department of Medical Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia.
authors: Maya
authors: M
authors: Chopra
authors: Department of Neurology, Sydney Children's Hospital, Randwick, New South Wales, Australia; The School of Women's and Children's Health, Medicine UNSW, University of New South Wales, Sydney, New South Wales, Australia.
authors: John A
authors: JA
authors: Lawson
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology; D000068338:Everolimus; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000150:complications*
chemical_list: D000927:Anticonvulsants; D000970:Antineoplastic Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus