Michael Cardamone1, Danny Flanagan2, David Mowat3, Sean E Kennedy4, Maya Chopra5, John A Lawson2. 1. 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. 2. 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. 3. 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. 4. 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. 5. Department of Medical Genetics, Sydney Children's Hospital, Randwick, New South Wales, Australia.
Abstract
OBJECTIVES: 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). STUDY DESIGN: 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). CONCLUSION: 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. Crown
OBJECTIVES: 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). STUDY DESIGN: 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). CONCLUSION: 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. Crown
Authors: Laura A Jansen; Ghayda M Mirzaa; Gisele E Ishak; Brian J O'Roak; Joseph B Hiatt; William H Roden; Sonya A Gunter; Susan L Christian; Sarah Collins; Carissa Adams; Jean-Baptiste Rivière; Judith St-Onge; Jeffrey G Ojemann; Jay Shendure; Robert F Hevner; William B Dobyns Journal: Brain Date: 2015-02-25 Impact factor: 13.501
Authors: Joel S Katz; Hyman Frankel; Tracy Ma; David Zagzag; Benjamin Liechty; Bruria Ben Zeev; Michal Tzadok; Orrin Devinsky; Howard L Weiner; Jonathan Roth Journal: Childs Nerv Syst Date: 2017-01-10 Impact factor: 1.475