Iwasaki Yasushi, Mori Keiko, Ito Masumi, Mimuro Maya, Kitamoto Tetsuyuki, Yoshida Mari
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
Department of Neurology, Oyamada Memorial Spa Hospital, Yokkaichi, Japan.
Neuropathology. 2017 Feb;37(1):78-85. doi: 10.1111/neup.12327. Epub 2016 Jul 20.
A 78-year-old Japanese man presented with rapidly progressive dementia and gait disturbances. Eight months before the onset of clinical symptoms, diffusion-weighted magnetic resonance imaging (DWI) demonstrated hyperintensities in the right temporal, right parietal and left medial occipital cortices. Two weeks after symptom onset, DWI showed extensive hyperintensity in the bilateral cerebral cortex, with regions of higher brightness that existed prior to symptom onset still present. Four weeks after clinical onset, periodic sharp wave complexes were identified on an electroencephalogram. Myoclonus was observed 8 weeks after clinical onset. The patient reached an akinetic mutism state and died 5 months after onset. Neuropathological examination showed widespread cerebral neocortical involvement of fine vacuole-type spongiform changes with large confluent vacuole-type spongiform changes. Spongiform degeneration with neuron loss and hypertrophic astrocytosis was also observed in the striatum and medial thalamus. The inferior olivary nucleus showed severe neuron loss with hypertrophic astrocytosis. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition with perivacuolar-type PrP deposition in the cerebral neocortex. Mild to moderate PrP deposition was also observed extensively in the basal ganglia, thalamus, cerebellum and brainstem, but it was not apparent in the inferior olivary nucleus. PrP gene analysis showed no mutations, and polymorphic codon 129 showed methionine homozygosity. Western blot analysis of protease-resistant PrP showed both type 1 scrapie type PrP (PrP ) and type 2 PrP . Based on the relationship between the neuroimaging and pathological findings, we speculated that cerebral cortical lesions with large confluent vacuoles and type 2 PrP would show higher brightness and continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrP . We believe the present patient had a combined form of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD), which suggests a broader spectrum of sCJD clinicopathological findings.
一名78岁的日本男性出现快速进展性痴呆和步态障碍。在临床症状出现前8个月，弥散加权磁共振成像（DWI）显示右侧颞叶、右侧顶叶和左侧枕叶内侧皮质高信号。症状出现后两周，DWI显示双侧大脑皮质广泛高信号，症状出现前就已存在的更高亮度区域依然存在。临床发病后4周，脑电图发现周期性锐波复合波。临床发病后8周观察到肌阵挛。患者进入无动性缄默状态，并在发病后5个月死亡。神经病理学检查显示广泛的大脑新皮质受累，有细泡型海绵状改变以及大融合泡型海绵状改变。纹状体和内侧丘脑也观察到伴有神经元丢失和肥大性星形细胞增多的海绵状变性。下橄榄核显示严重的神经元丢失和肥大性星形细胞增多。朊蛋白（PrP）免疫染色显示大脑新皮质广泛存在突触型PrP沉积以及空泡周围型PrP沉积。基底节、丘脑、小脑和脑干也广泛观察到轻度至中度PrP沉积，但在下橄榄核不明显。PrP基因分析未发现突变，多态密码子129显示甲硫氨酸纯合性。蛋白酶抗性PrP的蛋白质印迹分析显示既有1型羊瘙痒病型PrP（PrP ）又有2型PrP 。基于神经影像学和病理结果之间的关系，我们推测，与有细泡和1型PrP的病变相比，有大融合空泡和2型PrP的大脑皮质病变在DWI上会显示更高亮度和持续高信号。我们认为该患者患有MM1 + MM2-皮质合并丘脑型散发性克雅氏病（sCJD）的联合形式，这提示sCJD临床病理结果的范围更广。
