Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Neuropathology. 2009 Dec;29(6):727-34. doi: 10.1111/j.1440-1789.2009.01016.x. Epub 2009 Apr 28.
In this study, we describe the clinicopathologic findings in a 68-year-old man with panencephalopathic-type CJD with a substitution from methionine to arginine at codon 232 (M232R) in the prion protein (PrP) gene and type 1 PrP. Initial symptoms of the patient were a rapidly progressive memory disturbance and disorientation. The patient showed myoclonus and periodic sharp-wave complexes on electroencephalogram in the early stages of disease. Diffusion-weighted MRI along with the presence of both neuron-specific enolase and 14-3-3 protein in the CSF showed similarities to classic-type sporadic CJD. The patient reached the akinetic mutism state 2 months following the onset of symptoms and died after 13 months. Neuropathologic examination revealed panencephalopathic-type CJD pathology including widespread neuron loss with severe hypertrophic astrocytosis and status spongiosus in the cerebral gray matter, particularly in the neocortex. Cerebral white matter and the cerebellum also showed severe involvement. Immunohistochemical staining for PrP showed diffuse gray matter staining, indicating synaptic-type PrP deposition without plaque-type. Two different clinical phenotypes of M232R CJD were recognized despite the presence of the same PrP genotype, and the present case is speculated to correspond to the rapid-type.
在这项研究中,我们描述了一例 68 岁男性患者的临床病理发现,该患者患有泛神经性朊病毒病型 CJD,朊病毒蛋白(PrP)基因中的密码子 232 由蛋氨酸突变为精氨酸(M232R),并存在 1 型 PrP。患者的初始症状为进行性记忆障碍和定向障碍。在疾病的早期阶段,患者出现肌阵挛和周期性尖波复合波的脑电图表现。弥散加权 MRI 以及脑脊液中神经元特异性烯醇化酶和 14-3-3 蛋白的存在与经典散发性 CJD 相似。患者在症状出现后 2 个月进入无动性缄默状态,并在 13 个月后死亡。神经病理学检查显示泛神经性朊病毒病型 CJD 病理学改变,包括大脑灰质中广泛的神经元丧失,伴有严重的肥大星形胶质细胞和海绵状变性,特别是在新皮质。大脑白质和小脑也有严重受累。PrP 的免疫组织化学染色显示弥漫性灰质染色,表明突触型 PrP 沉积而无斑块型。尽管存在相同的 PrP 基因型,但仍识别出两种不同的 M232R CJD 临床表型,推测本病例对应于快速型。