Schwabe M J, Dobyns W B, Burke B, Armstrong D L
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, USA.
Pediatr Neurol. 1997 May;16(4):337-43. doi: 10.1016/s0887-8994(97)00030-1.
Alpers disease is a neurodegenerative disorder of childhood characterized by early developmental delay, intractable seizures, and death in childhood. Neuropathologic changes are most severe in the gray matter and consist of diffuse neuronal loss, spongiform changes, and astrocytosis. We report 2 siblings with Alpers disease who were discordant for exposure to valproate (VPA). Both had developmental delay, and a progressive seizure disorder beginning at 5 years of age. The proband died at age 8 years of complications of ongoing seizures, including epilepsia partialis continua, with only minimal liver abnormalities. Her younger brother was treated with VPA for new-onset seizures and developed fulminant liver failure 6 months later, which led to his death at 5 years of age. Neuropathologic abnormalities of both siblings were consistent with Alpers disease. These observations support classification of Alpers disease and Alpers disease with liver cirrhosis as a single disease. They also confirm previous reports indicating that VPA may accelerate fulminant liver failure in Alpers disease. We recommend that a diagnosis of Alpers disease be considered in children with unexplained early developmental delay, cerebellar signs, or partial seizures, especially epilepsia partialis continua. When Alpers disease is strongly suspected, use of VPA should be avoided.
阿尔珀斯病是一种儿童期神经退行性疾病，其特征为早期发育迟缓、难治性癫痫发作以及儿童期死亡。神经病理学改变在灰质中最为严重，包括弥漫性神经元丢失、海绵状改变和星形细胞增生。我们报告了2例患阿尔珀斯病的同胞，他们在丙戊酸盐（VPA）暴露方面存在差异。两人均有发育迟缓，且在5岁时开始出现进行性癫痫障碍。先证者在8岁时死于持续性癫痫发作的并发症，包括持续性部分性癫痫，肝脏仅有轻微异常。她的弟弟因新发癫痫接受VPA治疗，6个月后发生暴发性肝衰竭，导致其在5岁时死亡。两名同胞的神经病理学异常均符合阿尔珀斯病。这些观察结果支持将阿尔珀斯病和伴有肝硬化的阿尔珀斯病归为单一疾病。它们还证实了先前的报告，即VPA可能会加速阿尔珀斯病患者的暴发性肝衰竭。我们建议，对于有不明原因的早期发育迟缓、小脑体征或部分性癫痫发作，尤其是持续性部分性癫痫的儿童，应考虑诊断为阿尔珀斯病。当高度怀疑阿尔珀斯病时，应避免使用VPA。
