Lee Hsiu-Fen, Chi Ching-Shiang, Tsai Chi-Ren
Division of Pediatric Neurology, Children's Medical Center, Taichung Veterans General Hospital, 1650, Taiwan Boulevard Sec. 4, Taichung 407, Taiwan; School of Medicine, Chung Shan Medical University, 110, Sec. 1, Jianguo N. Rd., Taichung 402, Taiwan; Division of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, 79-9, Sha-Luen Hu Xi-Zhou Li Hou-Loung Town, Miaoli 356, Taiwan.
Division of Pediatric Neurology, Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, 699, Taiwan Boulevard Sec. 8, Wuchi, Taichung 435, Taiwan; School of Medicine, Chung Shan Medical University, 110, Sec. 1, Jianguo N. Rd., Taichung 402, Taiwan; College of Life Sciences, National Chung Hsing University, 250, Kuo Kuang Rd., Taichung 402, Taiwan; Division of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, 79-9, Sha-Luen Hu Xi-Zhou Li Hou-Loung Town, Miaoli 356, Taiwan.
Brain Dev. 2020 May;42(5):393-401. doi: 10.1016/j.braindev.2020.02.005. Epub 2020 Mar 12.
The aim of this study was to describe the electroclinical variability of four Taiwanese patients with pyridoxine-dependent epilepsy (PDE) caused by ALDH7A1 gene mutations.
Demographic data, case histories, clinical seizure patterns, EEG features, neuroimaging findings, ALDH7A1 gene mutations, treatments, and neurodevelopmental outcomes of the four patients were collected and analyzed.
The four patients exhibited the first symptom between the ages of 6 days and 11 months. The age of diagnosis was between 2 months and 13 years 8 months. Patient 1 exhibited classical phenotype of PDE, neonatal onset epileptic encephalopathy. Patient 2 showed atypical phenotypes of intractable epilepsy with additional neurological and abdominal symptoms. Patients 3 and 4, who had normal neurodevelopment, had familial epilepsy with fever sensitivity. Patients 2, 3, and 4 had atypical phenotypes and showed seizure exacerbation during febrile infections. EEG features of patient 1 revealed alternating rhythmic discharges followed by electrodecremental episodes; while those of patients 2, 3, and 4 disclosed nonspecific findings or normal results. Administration of oral pyridoxine hydrochloride resulted in seizure cessation in patients 1, 3, and 4, and they achieved normal neurodevelopmental outcomes, but intractable epilepsy and profound mental retardation occurred in patient 2 as he was not diagnosed until he was 13 years and 8 months old.
Electroclinical features of PDE vary widely, including patients with normal neurodevelopment and normal or nonspecific EEG findings. To avoid delay in treatment, a therapeutic trial with pyridoxine hydrochloride should be performed in all cases of neonatal, infantile, and childhood refractory epilepsy until ALDH7A1 gene mutation-related PDE has been excluded. Pyridoxine treatment may show clinical effectiveness even in a relatively late stage, i.e., age older than one year.
本研究旨在描述4例由ALDH7A1基因突变引起的吡哆醇依赖性癫痫（PDE）台湾患者的电临床变异性。
收集并分析了这4例患者的人口统计学数据、病史、临床发作模式、脑电图特征、神经影像学检查结果、ALDH7A1基因突变、治疗情况及神经发育结局。
4例患者的首发症状出现在6日龄至11月龄之间。诊断年龄在2月龄至13岁8月龄之间。患者1表现出PDE的经典表型，即新生儿期起病的癫痫性脑病。患者2表现出难治性癫痫的非典型表型，并伴有其他神经和腹部症状。神经发育正常的患者3和患者4患有热性敏感的家族性癫痫。患者2、3和4具有非典型表型，在发热感染期间癫痫发作加剧。患者1的脑电图特征显示为交替性节律性放电，随后是电极递减发作；而患者2、3和4的脑电图特征显示为非特异性表现或正常结果。口服盐酸吡哆醇使患者1、3和4的癫痫发作停止，他们实现了正常的神经发育结局，但患者2因直到13岁8月龄才被诊断，出现了难治性癫痫和严重智力障碍。
PDE的电临床特征差异很大，包括神经发育正常且脑电图表现正常或非特异性的患者。为避免治疗延误，对于所有新生儿、婴儿和儿童难治性癫痫病例，在排除ALDH7A1基因突变相关的PDE之前，均应进行盐酸吡哆醇治疗试验。即使在相对较晚的阶段，即年龄超过1岁时，吡哆醇治疗也可能显示出临床疗效。
