Sirolimus treatment is effective in children with TSC and epilepsy
Li-PingZou, Director, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China; Department of Pediatrics,Zouliping21@hotmail.com
Yu-Tian Liu, Beijing, China
Submitted October 05, 2016
We read with interest the article by Overwater et al. which showed that sirolimus did not significantly reduce seizure frequency in children with tuberous sclerosis complex (TSC) and intractable epilepsy. [1] TSC/mammalian target of rapamycin (mTOR) signaling is involved in regulating cell proliferation, synaptogenesis, and growth of dendrites and axons. [2,3] This suggests that any treatment aimed at correcting TSC-related epilepsy would need to be initiated during important developmental time windows.
We conducted a study of epilepsy in 52 children with TSC. [4] The median age was 25 months (vs 66 months in the Overwater et al. study) [1] and the patients received treatment for at least 24 weeks. The daily dose of sirolimus in our study was 0.2-1.0 mg, which is lower than in the Overwater et al. study (0.9-8.0 mg). [1] 25% of the sirolimus-treated patients in our study became seizure-free and the total effective rates per treatment period were 73% after 24 weeks, 74% after 48 weeks, 76% after 72 weeks, and 74% after 96 weeks. [4] Sirolimus treatment showed a certain effect on seizures, good safety, and was effective in children with TSC and epilepsy with few adverse reactions. [4] Further studies on this drug in controlling epilepsy in children with TSC are necessary.
1. Overwater IE, Rietman AB, Bindels-de Heus K, et al. Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology 2016;87:1011-1018.
2. Hentges KE, Sirry B, Gingeras AC, et al. FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse. Proc Natl Acad Sci U S A 2001;98:13796-13801.
3. Chow DK, Groszer M, Pribadi M, et al. Laminar and compartmental regulation of dendritic growth in mature cortex. Nat Neurosci 2009;12:116-118.
4. Zou L, Liu Y, Pang L, et al. [Efficacy and safety of rapamycin in treatment of children with
epilepsy complicated with tuberous sclerosis]. Zhonghua Er Ke Za Zhi 2014;52:812-816.
For disclosures, please contact the editorial office at journal@neurology.org.
We read with interest the article by Overwater et al. which showed that sirolimus did not significantly reduce seizure frequency in children with tuberous sclerosis complex (TSC) and intractable epilepsy. [1] TSC/mammalian target of rapamycin (mTOR) signaling is involved in regulating cell proliferation, synaptogenesis, and growth of dendrites and axons. [2,3] This suggests that any treatment aimed at correcting TSC-related epilepsy would need to be initiated during important developmental time windows.
We conducted a study of epilepsy in 52 children with TSC. [4] The median age was 25 months (vs 66 months in the Overwater et al. study) [1] and the patients received treatment for at least 24 weeks. The daily dose of sirolimus in our study was 0.2-1.0 mg, which is lower than in the Overwater et al. study (0.9-8.0 mg). [1] 25% of the sirolimus-treated patients in our study became seizure-free and the total effective rates per treatment period were 73% after 24 weeks, 74% after 48 weeks, 76% after 72 weeks, and 74% after 96 weeks. [4] Sirolimus treatment showed a certain effect on seizures, good safety, and was effective in children with TSC and epilepsy with few adverse reactions. [4] Further studies on this drug in controlling epilepsy in children with TSC are necessary.
1. Overwater IE, Rietman AB, Bindels-de Heus K, et al. Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology 2016;87:1011-1018.
2. Hentges KE, Sirry B, Gingeras AC, et al. FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse. Proc Natl Acad Sci U S A 2001;98:13796-13801.
3. Chow DK, Groszer M, Pribadi M, et al. Laminar and compartmental regulation of dendritic growth in mature cortex. Nat Neurosci 2009;12:116-118.
4. Zou L, Liu Y, Pang L, et al. [Efficacy and safety of rapamycin in treatment of children with epilepsy complicated with tuberous sclerosis]. Zhonghua Er Ke Za Zhi 2014;52:812-816.
For disclosures, please contact the editorial office at journal@neurology.org.