Wolf Nicole I, Rahman Shamima, Schmitt Bernhard, Taanman Jan-Willem, Duncan Andrew J, Harting Inga, Wohlrab Gabriele, Ebinger Friedrich, Rating Dietz, Bast Thomas
Pediatric Neurology, University Children's Hospital, Heidelberg, Germany.
Epilepsia. 2009 Jun;50(6):1596-607. doi: 10.1111/j.1528-1167.2008.01877.x. Epub 2008 Nov 19.
Refractory convulsive status epilepticus in infancy and childhood is a rare emergency situation. Metabolic disorders frequently underlie this condition, in particular Alpers' disease caused by POLG1 mutations. Status epilepticus may be the first symptom. A pathognomonic electroencephalography (EEG) signature may facilitate diagnosis of Alpers' disease and allow timely avoidance of valproic acid, which is contraindicated in this disorder because it may trigger fatal liver failure.
We present five patients with Alpers' disease caused by mutations in POLG1. Age of onset ranged from 7 months to 10 years. Three of the five children died after 3 to 12 months after onset of status epilepticus. Two of these had liver failure associated with use of valproic acid; liver transplantation in one child did not prevent a fatal neurologic outcome.
Convulsive status epilepticus was the first obvious sign of Alpers' disease in all children. All had focal clonic and complex-focal seizures; four of them developed epilepsia partialis continua. In four children, initial EEG showed unilateral occipital rhythmic high-amplitude delta with superimposed (poly)spikes (RHADS). Magnetic resonance imaging (MRI) revealed cortical and thalamic involvement in all, although there were only discrete abnormalities in one child. Metabolic investigations remained normal in three children.
Alpers' disease is an important differential diagnosis in childhood refractory convulsive status epilepticus. Its EEG hallmark of RHADS is important for timely diagnosis, management, and counseling.
婴幼儿和儿童难治性惊厥性癫痫持续状态是一种罕见的紧急情况。代谢紊乱常常是这种情况的基础，特别是由POLG1突变引起的阿尔珀斯病。癫痫持续状态可能是首发症状。一种具有诊断特征的脑电图（EEG）特征可能有助于阿尔珀斯病的诊断，并能及时避免使用丙戊酸，因为在这种疾病中丙戊酸是禁忌的，它可能引发致命的肝衰竭。
我们报告了5例由POLG1突变引起的阿尔珀斯病患者。发病年龄从7个月到10岁不等。5名儿童中有3名在癫痫持续状态发作后3至12个月死亡。其中2名患者的肝衰竭与使用丙戊酸有关；1名儿童接受肝移植也未能避免致命的神经学结局。
惊厥性癫痫持续状态是所有儿童阿尔珀斯病的首个明显症状。所有患者均有局灶性阵挛性发作和复杂局灶性发作；其中4例发展为持续性部分性癫痫。4名儿童的初始脑电图显示单侧枕部有节律性高幅δ波并伴有叠加（多）棘波（RHADS）。磁共振成像（MRI）显示所有患者均有皮质和丘脑受累，尽管只有1名儿童有离散性异常。3名儿童的代谢检查结果仍正常。
阿尔珀斯病是儿童难治性惊厥性癫痫持续状态的重要鉴别诊断。其EEG特征性表现RHADS对及时诊断、治疗和咨询具有重要意义。
