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Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age

INTRODUCTION: Mechanistic target of rapamycin (mTOR) inhibitors sirolimus and everolimus are an effective therapy for subependymal giant cell astrocytomas, cardiac rhabdomyomas, renal angiomyolipomas, and lymphangioleiomyomatosis associated with tuberous sclerosis complex (TSC). Everolimus was recen...

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Autores principales: Śmiałek, Dominika, Kotulska, Katarzyna, Duda, Aleksandra, Jóźwiak, Sergiusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195938/
https://www.ncbi.nlm.nih.gov/pubmed/37085686
http://dx.doi.org/10.1007/s40120-023-00476-7
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author Śmiałek, Dominika
Kotulska, Katarzyna
Duda, Aleksandra
Jóźwiak, Sergiusz
author_facet Śmiałek, Dominika
Kotulska, Katarzyna
Duda, Aleksandra
Jóźwiak, Sergiusz
author_sort Śmiałek, Dominika
collection PubMed
description INTRODUCTION: Mechanistic target of rapamycin (mTOR) inhibitors sirolimus and everolimus are an effective therapy for subependymal giant cell astrocytomas, cardiac rhabdomyomas, renal angiomyolipomas, and lymphangioleiomyomatosis associated with tuberous sclerosis complex (TSC). Everolimus was recently approved in the EU and the USA for the treatment of refractory focal-onset seizures. Despite frequent use of mTOR inhibitors, there are only a few studies on their effect on epilepsy control in children under 2 years of age. This study aims to assess the effect of adjunctive mTOR inhibitor treatment on seizure frequency in this age group. METHODS: We performed retrospective data analysis of medical records of patients with TSC who initiated sirolimus or everolimus under the age of 2 years. Participants’ antiseizure medication was adjusted according to their epilepsy control independently from mTOR inhibitor administration. The data was assessed separately for patients treated with mTOR inhibitors before and after the onset of seizures. We also compared the treatment group with a matched control group. The follow-up duration was up to 24 months. RESULTS: Twenty-one patients with TSC from two clinical centers were included in the study. Nine participants had no history of seizures before mTOR inhibitor initiation. Twelve reported active epilepsy in the month prior to treatment initiation. Most patients treated preventively with mTOR inhibitors did not report active epilepsy at the end of their follow-up. In the second group, the mean frequency of seizures decreased with time. According to the comparative analysis, seizure control was better in the groups treated with mTOR inhibitors. CONCLUSION: Patients with TSC treated with mTOR inhibitors demonstrated better seizure control than individuals without this treatment. Adjunctive pharmacotherapy with mTOR inhibitors appears to have a beneficial effect on epilepsy outcome in young children. Further prospective clinical trials should be conducted to determine the efficacy of mTOR inhibitors on epilepsy in patients with TSC under the age of 2 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-023-00476-7.
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spelling pubmed-101959382023-05-20 Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age Śmiałek, Dominika Kotulska, Katarzyna Duda, Aleksandra Jóźwiak, Sergiusz Neurol Ther Original Research INTRODUCTION: Mechanistic target of rapamycin (mTOR) inhibitors sirolimus and everolimus are an effective therapy for subependymal giant cell astrocytomas, cardiac rhabdomyomas, renal angiomyolipomas, and lymphangioleiomyomatosis associated with tuberous sclerosis complex (TSC). Everolimus was recently approved in the EU and the USA for the treatment of refractory focal-onset seizures. Despite frequent use of mTOR inhibitors, there are only a few studies on their effect on epilepsy control in children under 2 years of age. This study aims to assess the effect of adjunctive mTOR inhibitor treatment on seizure frequency in this age group. METHODS: We performed retrospective data analysis of medical records of patients with TSC who initiated sirolimus or everolimus under the age of 2 years. Participants’ antiseizure medication was adjusted according to their epilepsy control independently from mTOR inhibitor administration. The data was assessed separately for patients treated with mTOR inhibitors before and after the onset of seizures. We also compared the treatment group with a matched control group. The follow-up duration was up to 24 months. RESULTS: Twenty-one patients with TSC from two clinical centers were included in the study. Nine participants had no history of seizures before mTOR inhibitor initiation. Twelve reported active epilepsy in the month prior to treatment initiation. Most patients treated preventively with mTOR inhibitors did not report active epilepsy at the end of their follow-up. In the second group, the mean frequency of seizures decreased with time. According to the comparative analysis, seizure control was better in the groups treated with mTOR inhibitors. CONCLUSION: Patients with TSC treated with mTOR inhibitors demonstrated better seizure control than individuals without this treatment. Adjunctive pharmacotherapy with mTOR inhibitors appears to have a beneficial effect on epilepsy outcome in young children. Further prospective clinical trials should be conducted to determine the efficacy of mTOR inhibitors on epilepsy in patients with TSC under the age of 2 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-023-00476-7. Springer Healthcare 2023-04-21 /pmc/articles/PMC10195938/ /pubmed/37085686 http://dx.doi.org/10.1007/s40120-023-00476-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research
Śmiałek, Dominika
Kotulska, Katarzyna
Duda, Aleksandra
Jóźwiak, Sergiusz
Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age
title Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age
title_full Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age
title_fullStr Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age
title_full_unstemmed Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age
title_short Effect of mTOR Inhibitors in Epilepsy Treatment in Children with Tuberous Sclerosis Complex Under 2 Years of Age
title_sort effect of mtor inhibitors in epilepsy treatment in children with tuberous sclerosis complex under 2 years of age
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195938/
https://www.ncbi.nlm.nih.gov/pubmed/37085686
http://dx.doi.org/10.1007/s40120-023-00476-7
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