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Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status

We investigated the effect of the mammalian target of rapamycin (mTOR) inhibitor everolimus on tuberous sclerosis complex- (TSC-) associated autistic symptoms and focal seizures with impaired awareness in a female child with TSC. We further evaluated the relationship between improved autistic sympto...

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Autores principales: Yui, Kunio, Imataka, George, Sasaki, Hitomi, Kawasaki, Yohei, Okanshi, Tohru, Shiroki, Ryoichi, Yoshihara, Shigemi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907049/
https://www.ncbi.nlm.nih.gov/pubmed/31871809
http://dx.doi.org/10.1155/2019/2070619
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author Yui, Kunio
Imataka, George
Sasaki, Hitomi
Kawasaki, Yohei
Okanshi, Tohru
Shiroki, Ryoichi
Yoshihara, Shigemi
author_facet Yui, Kunio
Imataka, George
Sasaki, Hitomi
Kawasaki, Yohei
Okanshi, Tohru
Shiroki, Ryoichi
Yoshihara, Shigemi
author_sort Yui, Kunio
collection PubMed
description We investigated the effect of the mammalian target of rapamycin (mTOR) inhibitor everolimus on tuberous sclerosis complex- (TSC-) associated autistic symptoms and focal seizures with impaired awareness in a female child with TSC. We further evaluated the relationship between improved autistic symptoms and seizures and increased the serum levels of the antioxidant proteins, ceruloplasmin (Cp) and transferrin (Tf), and oxidant-antioxidant status indicated by the oxidant marker oxidized low-density lipoprotein (ox-LDL) and the antioxidant marker total antioxidant power (TAP). Everolimus treatment improved impaired social cognition and autistic behaviors; however, seizure and epileptic activity persisted. Serum Cp and Tf levels gradually increased in response to improved autistic symptoms. Serum TAP levels gradually decreased from baseline to the lowest value at 16 weeks and then increased at 24 weeks, showing a trend toward decreased total score of the Aberrant Behavior Checklist. This study revealed that everolimus treatment improved impaired social cognition with increased serum levels of the copper mediator (Cp) and iron mediator (Tf) via homeostatic control of mTOR activity accompanied by overlap of the oxidant-antioxidant system. Everolimus had no effect on TSC-related epileptiform discharges, and thus, the autistic symptoms and epileptic activity may be two independent end results of a common central nervous system disorder including mTOR hyperactivity. This trial is registered with JMAS-IIA00258.
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spelling pubmed-69070492019-12-23 Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status Yui, Kunio Imataka, George Sasaki, Hitomi Kawasaki, Yohei Okanshi, Tohru Shiroki, Ryoichi Yoshihara, Shigemi Case Rep Pediatr Case Report We investigated the effect of the mammalian target of rapamycin (mTOR) inhibitor everolimus on tuberous sclerosis complex- (TSC-) associated autistic symptoms and focal seizures with impaired awareness in a female child with TSC. We further evaluated the relationship between improved autistic symptoms and seizures and increased the serum levels of the antioxidant proteins, ceruloplasmin (Cp) and transferrin (Tf), and oxidant-antioxidant status indicated by the oxidant marker oxidized low-density lipoprotein (ox-LDL) and the antioxidant marker total antioxidant power (TAP). Everolimus treatment improved impaired social cognition and autistic behaviors; however, seizure and epileptic activity persisted. Serum Cp and Tf levels gradually increased in response to improved autistic symptoms. Serum TAP levels gradually decreased from baseline to the lowest value at 16 weeks and then increased at 24 weeks, showing a trend toward decreased total score of the Aberrant Behavior Checklist. This study revealed that everolimus treatment improved impaired social cognition with increased serum levels of the copper mediator (Cp) and iron mediator (Tf) via homeostatic control of mTOR activity accompanied by overlap of the oxidant-antioxidant system. Everolimus had no effect on TSC-related epileptiform discharges, and thus, the autistic symptoms and epileptic activity may be two independent end results of a common central nervous system disorder including mTOR hyperactivity. This trial is registered with JMAS-IIA00258. Hindawi 2019-11-23 /pmc/articles/PMC6907049/ /pubmed/31871809 http://dx.doi.org/10.1155/2019/2070619 Text en Copyright © 2019 Kunio Yui et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Report
Yui, Kunio
Imataka, George
Sasaki, Hitomi
Kawasaki, Yohei
Okanshi, Tohru
Shiroki, Ryoichi
Yoshihara, Shigemi
Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status
title Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status
title_full Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status
title_fullStr Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status
title_full_unstemmed Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status
title_short Improvement in Impaired Social Cognition but Not Seizures by Everolimus in a Child with Tuberous Sclerosis-Associated Autism through Increased Serum Antioxidant Proteins and Oxidant/Antioxidant Status
title_sort improvement in impaired social cognition but not seizures by everolimus in a child with tuberous sclerosis-associated autism through increased serum antioxidant proteins and oxidant/antioxidant status
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907049/
https://www.ncbi.nlm.nih.gov/pubmed/31871809
http://dx.doi.org/10.1155/2019/2070619
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