Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute.
Neuropathology. 2013 Oct;33(5):568-75. doi: 10.1111/neup.12013. Epub 2013 Jan 16.
A 68-year-old Japanese man gradually showed abnormal behavior and gait disturbance with bradykinesia. Slowly progressive dementia, including memory disturbance and disorientation, was also observed. Cerebral cortical hyperintensity on diffusion-weighted MRI was observed 6 months after onset. The patient progressed to an akinetic mutism state with mild myoclonus, and atypical periodic sharp-wave complexes were observed by electroencephalogram 13 months after onset. He was clinically suspected of having atypical CJD and died after 19 months total disease duration. The brain weighed 1160 g and showed mild atrophy of the cerebrum and cerebellum with ventricular dilatation. Spongiform changes with varying vacuole size and gliosis was extensive in the cerebral cortex and basal ganglia. Neuron loss in the cerebral cortex, basal ganglia and thalamus was relatively mild. The cerebellum showed mild spongiform changes of the molecular layer and mild neuron loss in the Purkinje cell layer. PrP immunostaining showed mainly coarse-type combined with diffuse synaptic-type PrP deposition in the cerebral gray matter. Some perivacuolar-type PrP deposition was also present. Numerous plaque-type PrP depositions were observed in the molecular layer of the cerebellum. Analysis of the PrP gene revealed a methionine-to-arginine (Met-to-Arg) substitution at codon 232 (M232R) with Met homozygosity at codon 129. Western blot analysis of protease-resistant PrP indicated type 2 dominant PrP combined with type 1. Genetic CJD with M232R substitution in the PrP gene has only been reported in Japan. Although two clinical phenotypes (rapid-type and slow-type) were suggested in the M232R CJD cases (despite the presence of the same PrP genotype), the pathological and molecular backgrounds have not been well understood because there have only been a few autopsied case reports. This is the first case report of M232R CJD presenting with 1 + 2 PrP.
一位 68 岁的日本男性逐渐出现异常行为和运动障碍伴运动迟缓。也观察到进行性痴呆，包括记忆障碍和定向障碍。发病 6 个月后，弥散加权 MRI 显示大脑皮质高信号。发病 13 个月后，患者进展为无动性缄默状态，伴有轻度肌阵挛，脑电图观察到非典型周期性尖波复合波。临床上疑诊为非典型 CJD，总病程 19 个月后死亡。脑重 1160g，大脑和小脑轻度萎缩伴脑室扩张。大脑皮质和基底节广泛存在海绵状改变，伴有不同大小的空泡和胶质增生。大脑皮质、基底节和丘脑神经元丢失相对较轻。小脑分子层轻度海绵状改变，浦肯野细胞层神经元丢失轻度。PrP 免疫染色显示主要为粗颗粒型，结合大脑灰质弥散型突触型 PrP 沉积。也存在一些围空泡型 PrP 沉积。小脑分子层观察到大量斑块型 PrP 沉积。PrP 基因分析显示 232 密码子处蛋氨酸到精氨酸（Met-to-Arg）取代（M232R），129 密码子处 Met 纯合。蛋白酶抗性 PrP 的 Western blot 分析表明 2 型优势 PrP 与 1 型结合。PrP 基因中 M232R 取代的遗传 CJD 仅在日本有报道。尽管 M232R CJD 病例中存在两种临床表型（快速型和缓慢型）（尽管存在相同的 PrP 基因型），但由于只有少数尸检病例报告，其病理和分子背景尚未得到很好的理解。这是首例 M232R CJD 呈 1+2 PrP 的病例报告。
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