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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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Case Reports in Pediatrics |
| Online Access: | http://dx.doi.org/10.1155/2019/2070619 |
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| author | Kunio Yui George Imataka Hitomi Sasaki Yohei Kawasaki Tohru Okanshi Ryoichi Shiroki Shigemi Yoshihara |
| author_facet | Kunio Yui George Imataka Hitomi Sasaki Yohei Kawasaki Tohru Okanshi Ryoichi Shiroki Shigemi Yoshihara |
| author_sort | Kunio Yui |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-d92799c0268944029d7531fff11ca386 |
| institution | Kabale University |
| issn | 2090-6803 2090-6811 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Pediatrics |
| spelling | doaj-art-d92799c0268944029d7531fff11ca3862025-02-03T01:10:40ZengWileyCase Reports in Pediatrics2090-68032090-68112019-01-01201910.1155/2019/20706192070619Improvement 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 StatusKunio Yui0George Imataka1Hitomi Sasaki2Yohei Kawasaki3Tohru Okanshi4Ryoichi Shiroki5Shigemi Yoshihara6Department of Urology, Fujita Health University School of Medicine, Aichi 470-1192, JapanDepartment of Pediatrics, Dokkyo Medical University, Mibu, Tochigi 321-0293, JapanDepartment of Urology, Fujita Health University School of Medicine, Aichi 470-1192, JapanClinical Research Center, Chiba University Hospital, Chiba 260-8677, JapanDepartment of Child Neurology, Seirei Hamamatsu General Hospital, Hamamatsu 430-8558, JapanDepartment of Urology, Fujita Health University School of Medicine, Aichi 470-1192, JapanDepartment of Pediatrics, Dokkyo Medical University, Mibu, Tochigi 321-0293, JapanWe 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.http://dx.doi.org/10.1155/2019/2070619 |
| spellingShingle | Kunio Yui George Imataka Hitomi Sasaki Yohei Kawasaki Tohru Okanshi Ryoichi Shiroki Shigemi Yoshihara 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 Case Reports in Pediatrics |
| 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 |
| url | http://dx.doi.org/10.1155/2019/2070619 |
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