Department of Preventive medical center, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
Department of Neuropathology (Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
Neuropathology. 2024 Aug;44(4):304-313. doi: 10.1111/neup.12964. Epub 2024 Feb 14.
Methionine/valine (MV) 2 type of sporadic Creutzfeldt-Jakob (sCJD) is divided into three subtypes based on neuropathological criteria: MV2-kuru (MV2K), MV2-cortical (MV2C), and MV2K + C, exhibiting the co-occurrence of these two pathological features. We report an autopsy case of MV2K + C subtype of sCJD. A 46-year-old Japanese man began to make mistakes at work. Two months later, he gradually developed gait instability. The initial neurological examination revealed limb ataxia and myoclonus. Diffusion-weighted images (DWI) showed a hyperintensity in the right frontal cortex, basal ganglia, and thalamus. Ten months after the onset of disease, he fell into akinetic mutism. He died at 47 years of age, 12 months after the initial presentation. Pathological investigation revealed microvacuolation and confluent vacuoles in the cerebral cortex. In the basal ganglia and thalamus, there was severe neuronal loss and gliosis with mild spongiform change. Kuru plaques were found within the cerebellum. Prion protein (PrP) immunostaining revealed synaptic, perivacuolar, perineuronal, and plaque-like deposits in the cerebral cortex. There were synaptic and plaque-like PrP deposits in the basal ganglia, thalamus, and granular cell layer of the cerebellum. In these areas, plaque-like deposits mainly consisted of small deposits, whereas plaque-like deposits in the cerebral cortex consisted both of coarse granular and small deposits. Analysis of the PrP gene showed no pathogenic mutations, and Western blot examination revealed a mixture of type 2 and intermediate-type PrP. The progressive cognitive decline and ataxia in addition to the hyperintensity in the basal ganglia and/or thalamus on DWI are the basis for clinical diagnosis of MV2. The severe gliosis in the basal ganglia and various morphologies of plaque-like deposits that differ by the region may be characteristic of MV2K + C. Detailed neuropathological examination together with Western blot analysis is important to collect more cases for elucidating the pathogenesis of MV2K + C.
蛋氨酸/缬氨酸（MV）2 型散发性克雅氏病（sCJD）根据神经病理学标准分为三种亚型：MV2-库鲁病（MV2K）、MV2-皮质（MV2C）和 MV2K+C，表现为这两种病理特征的共同发生。我们报告一例 MV2K+C 型 sCJD 的尸检病例。一名 46 岁的日本男性开始在工作中犯错。两个月后，他逐渐出现步态不稳。最初的神经系统检查显示四肢共济失调和肌阵挛。弥散加权成像（DWI）显示右侧额叶皮质、基底节和丘脑存在高信号。疾病发作后 10 个月，他陷入无动性缄默状态。他在发病后 12 个月，即 47 岁时死亡。病理检查显示大脑皮质出现微空泡和融合空泡。基底节和丘脑可见严重的神经元丢失和胶质增生，伴有轻度海绵状改变。小脑内可见库鲁斑块。朊蛋白（PrP）免疫染色显示大脑皮质存在突触、空泡周围、神经周围和斑块样沉积物。基底节、丘脑和小脑颗粒细胞层均存在突触和斑块样 PrP 沉积物。在这些区域，斑块样沉积物主要由小沉积物组成，而大脑皮质的斑块样沉积物既有粗颗粒状也有小沉积物。PrP 基因分析未发现致病性突变，Western blot 检查显示存在 2 型和中间型 PrP 的混合物。除 DWI 上基底节和/或丘脑的高信号外，进行性认知下降和共济失调是 MV2 的临床诊断基础。基底节严重的神经胶质增生和斑块样沉积物的各种形态，不同区域可能存在差异，这可能是 MV2K+C 的特征。详细的神经病理学检查结合 Western blot 分析对于收集更多病例以阐明 MV2K+C 的发病机制非常重要。
