d'Orsi Giuseppe, Specchio Luigi M
Department of Neurological Sciences, Epilepsy Centre, Clinic of Nervous System Diseases, Ospedali Riuniti Foggia, University of Foggia, Via Luigi Pinto 1, 71100, Foggia, Italy,
J Neurol. 2014 Aug;261(8):1584-97. doi: 10.1007/s00415-014-7376-x. Epub 2014 Jun 4.
This study aimed to elucidate the natural history of senile myoclonic epilepsy, a type of myoclonic epilepsy associated with Alzheimer's disease in adult Down syndrome patients. Twelve Down syndrome patients over the age of 40 years with myoclonic epilepsy and Alzheimer's disease underwent clinical, neuropsychological, neurophysiological, and neuroradiological study. The kariotypes, APOE polymorphisms, all exons in the PSEN1 and PSEN2 genes, and exons 16 and 17 in the APP gene were determined for all patients. CSF Aβ42, p-tau181, and t-tauAg were determined for two patients. Three main stages appeared during the course of the syndrome. The first stage was characterized by dementia onset (mean age: 51 ± 6.6 years), diffuse EEG abnormalities during sleep, and cerebral atrophy determined using neuroimaging. During the second stage, myoclonic epilepsy manifested (mean age: 51.4 ± 7.2 years) with myoclonic jerks time-locked to diffuse epileptiform abnormalities upon awakening, which was controlled with antiepileptic drugs. During the third stage (mean age: 54.8 ± 7.6 years), myoclonic seizures were replaced with nonepileptic myoclonus, and cerebellar signs, severe dementia, and photosensitivity developed. All patients showed complete trisomy 21. Mutations were ruled out on the APP, PSEN1, and PSEN2 genes, and APOE analysis revealed ε3/ε3 homozygosity. CSF biomarkers showed a decrease in Aβ42 and an increase in p-tau181. The natural history of senile myoclonic epilepsy is consistent with progressive myoclonus epilepsy. Chromosome 21 is implicated in its pathophysiology; however, other genetic and/or environmental risk factors cannot be excluded. The absence of the APOE type 4 allele could predict its progression.
本研究旨在阐明老年肌阵挛性癫痫的自然病史，这是一种与成年唐氏综合征患者阿尔茨海默病相关的肌阵挛性癫痫类型。12例年龄超过40岁、患有肌阵挛性癫痫和阿尔茨海默病的唐氏综合征患者接受了临床、神经心理学、神经生理学和神经放射学研究。测定了所有患者的核型、载脂蛋白E（APOE）多态性、早老素1（PSEN1）基因和早老素2（PSEN2）基因的所有外显子，以及淀粉样前体蛋白（APP）基因的第16和17外显子。对两名患者测定了脑脊液β淀粉样蛋白42（Aβ42）、磷酸化tau蛋白181（p-tau181）和总tau抗原（t-tauAg）。该综合征病程中出现三个主要阶段。第一阶段的特征为痴呆起病（平均年龄：51±6.6岁）、睡眠期间脑电图弥漫性异常以及神经影像学检查显示脑萎缩。在第二阶段，肌阵挛性癫痫出现（平均年龄：51.4±7.2岁），肌阵挛抽搐与觉醒时弥漫性癫痫样异常时间锁定，可通过抗癫痫药物控制。在第三阶段（平均年龄：54.8±7.6岁），肌阵挛发作被非癫痫性肌阵挛取代，出现小脑体征、严重痴呆和光敏性。所有患者均显示21号染色体完全三体。排除了APP、PSEN1和PSEN2基因的突变，APOE分析显示ε3/ε3纯合子。脑脊液生物标志物显示Aβ42降低和p-tau181升高。老年肌阵挛性癫痫的自然病史与进行性肌阵挛性癫痫一致。21号染色体与其病理生理学有关；然而，不能排除其他遗传和/或环境危险因素。APOE 4型等位基因的缺失可预测其进展。
