Makiko Saitoh1, Mayu Shinohara2, Atsushi Ishii3, Yukiko Ihara3, Shinichi Hirose3, Masashi Shiomi4, Hisashi Kawawaki5, Masaya Kubota6, Takanori Yamagata7, Akie Miyamoto8, Gaku Yamanaka9, Kaoru Amemiya10, Kenjiro Kikuchi11, Atsushi Kamei12, Manami Akasaka12, Yuki Anzai13, Masashi Mizuguchi2. 1. Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Japan. Electronic address: makisaito-tky@umin.ac.jp. 2. Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Japan. 3. Department of Pediatrics, Fukuoka University, Japan. 4. Department of Pediatrics, Child Medical Center, Osaka City General Hospital, Japan. 5. Department of Pediatric Neurology, Child Medical Center, Osaka City General Hospital, Japan. 6. Department of Neurology, National Center for Child Health and Development, Japan. 7. Department of Pediatrics, Jichi Medical University, Japan. 8. Department of Pediatrics, Asahikawa Habilitation Center for Disabled Children, Japan. 9. Department of Pediatrics, Tokyo Medical University, Japan. 10. Department of Neurology, Tokyo Metropolitan Hachioji Children's Hospital, Japan. 11. Division of Neurology, Saitama Children's Medical Center, Japan. 12. Department of Pediatrics, Iwate Medical University, Japan. 13. Department of Pediatrics, Saiseikai Yokohamashi Tobu Hospital, Japan.
Abstract
BACKGROUND: Theophylline has recently been suspected as a risk factor of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), although there has been no systematic study on the relationship between acute encephalopathy in children taking theophylline (AET) and AESD. METHODS: We recruited 16 Japanese patients (11 male and 5 female, median age of 2 years and 7 months) with AET from 2008 to 2013. We evaluated their clinical features, such as the duration of first seizure, biphasic clinical course and cranial CT/MRI imaging and compared them with those of AESD. We analyzed the polymorphisms or mutations of genes which are associated with AESD. RESULTS: Clinically, 12 patients had neurological and/or radiological features of AESD. Only one patient died, whereas all 15 surviving patients were left with motor and/or intellectual deficits. Genetically, 14 patients had at least one of the following polymorphisms or mutations associated with AESD: thermolabile variation of the carnitine palmitoyltransferase 2 (CPT2) gene, polymorphism causing high expression of the adenosine receptor A2A (ADORA2A) gene, and heterozygous missense mutation of the voltage gated sodium channel 1A (SCN1A) and 2A (SCN2A) gene. CONCLUSIONS: Our results demonstrate that AET overlaps with AESD, and that AET is a multifactorial disorder sharing a genetic background with AESD.
BACKGROUND:Theophylline has recently been suspected as a risk factor of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), although there has been no systematic study on the relationship between acute encephalopathy in children taking theophylline (AET) and AESD. METHODS: We recruited 16 Japanese patients (11 male and 5 female, median age of 2 years and 7 months) with AET from 2008 to 2013. We evaluated their clinical features, such as the duration of first seizure, biphasic clinical course and cranial CT/MRI imaging and compared them with those of AESD. We analyzed the polymorphisms or mutations of genes which are associated with AESD. RESULTS: Clinically, 12 patients had neurological and/or radiological features of AESD. Only one patientdied, whereas all 15 surviving patients were left with motor and/or intellectual deficits. Genetically, 14 patients had at least one of the following polymorphisms or mutations associated with AESD: thermolabile variation of the carnitine palmitoyltransferase 2 (CPT2) gene, polymorphism causing high expression of the adenosine receptor A2A (ADORA2A) gene, and heterozygous missense mutation of the voltage gated sodium channel 1A (SCN1A) and 2A (SCN2A) gene. CONCLUSIONS: Our results demonstrate that AET overlaps with AESD, and that AET is a multifactorial disorder sharing a genetic background with AESD.
Authors: Esmé J Baan; Veronique A de Smet; Christina E Hoeve; Alexandra C Pacurariu; Miriam C J M Sturkenboom; Johan C de Jongste; Hettie M Janssens; Katia M C Verhamme Journal: Drug Saf Date: 2020-01 Impact factor: 5.606