An autopsied case of V180I Creutzfeldt-Jakob disease presenting with panencephalopathic-type pathology and a characteristic prion protein type
An autopsied case of V180I Creutzfeldt-Jakob disease presenting with panencephalopathic-type pathology and a characteristic prion protein type
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DOI：
10.1111/j.1440-1789.2010.01192.x
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发表时间：
2011-10-01
期刊：
影响因子：
2.3
通讯作者：
Hashizume, Yoshio
中科院分区：
文献类型：
--
作者：
Iwasaki, Yasushi;Mori, Keiko;Hashizume, Yoshio
一位73岁的日本女性表现为缓慢进行性失语症、失用症和痴呆。她没有朊病毒病或痴呆家族史。一年后，她表现出帕金森病，最初怀疑为皮质基底变性。MRI表现为初始t2加权图像左侧颞叶新皮层肿胀，弥漫性加权图像后可见大脑皮层高信号区。患者在发病后15个月和22个月分别出现肌阵挛和运动性缄默症。连续脑电图未见周期性锐波复合体。朊蛋白（PrP）基因分析显示，在密码子180处存在缬氨酸与异亮氨酸点突变，在密码子129处存在蛋氨酸纯合。该患者临床症状及病程不典型，经鼻管喂养后病情稳定数年。她在发病102个月后死于呼吸衰竭，享年81岁。尸检显示广泛的海绵状变性伴弱突触型PrP沉积，证实了遗传性CJD的诊断。这种长期疾病的大脑皮层神经元数量相对保留，肥厚性星形细胞增生一般为中度，但脑白质表现为弥漫性严重髓磷脂苍白，组织稀疏，提示泛脑病型病理。小脑皮层保存较好，分子层有轻度海绵状改变，浦肯野神经元层有中度神经元丢失，PrP呈散在小斑块样沉积。蛋白酶抗性PrP的Western blot分析显示没有二糖异构体带的特征模式。V180I CJD是一种有趣的遗传性CJD形式，涉及临床病理，分子和遗传学的发现。
A 73-year-old Japanese woman showed slowly progressive aphasia, apraxia and dementia. She had no family history of prion disease or dementia. One year later she showed parkinsonism and corticobasal degeneration was initially suspected. On MRI, the left temporal neocortex seemed swollen on T2-weighted images in the initial stage, and a later high-signal intensity region was observed in the cerebral cortex in diffusion-weighted images. The patient developed myoclonus and an akinetic mutism state 15 months and 22 months after onset, respectively. Consecutive electroencephalography revealed no periodic sharp-wave complexes. Prion protein (PrP) gene analysis revealed a valine to isoleucine point mutation at codon 180, and methionine homozygosity at codon 129. This patient's clinical symptoms and disease course were atypical for Creutzfeldt-Jakob disease (CJD), and a stable state with nasal tube-feeding lasted several years. She died of respiratory failure at the age of 81, 102 months after the onset. Autopsy revealed widespread spongiform degeneration with weak synaptic-type PrP deposition, confirming the diagnosis of genetic CJD. Neurons in the cerebral cortex were relatively preserved in number and hypertrophic astrocytosis was generally moderate for such long-term disease, but cerebral white matter showed diffuse severe myelin pallor with tissue rarefaction suggestive of panencephalopatic-type pathology. The cerebellar cortex was relatively well preserved with observation of mild spongiform change in the molecular layer, moderate neuron loss in the Purkinje neuron layer, and scattered small plaque-like PrP deposition. Western blot analysis of protease-resistant PrP showed a characteristic pattern without a diglycoform band. V180I CJD is an interesting form of genetic CJD with regards to the clinicopathologic, molecular and genetic findings.