Cerebral cortex swelling in V180I genetic Creutzfeldt–Jakob disease: comparative imaging study between sporadic and V180I genetic Creutzfeldt–Jakob disease in the early stage

The most common genetic Creutzfeldt-Jakob disease (gCJD) in Japan is caused by a point mutation in which isoleucine replaces valine at codon 180 of the prion protein (<i>PrP</i>) gene (V180I gCJD). Evidence suggests that cerebral cortex swelling, which appears as abnormal hyperintensities on diffusion-weighted imaging (DWI), is a characteristic magnetic resonance imaging (MRI) finding of V180I gCJD. However, no study has directly compared the MRI findings between V180I gCJD and sporadic CJD (sCJD). The current study, therefore, aims to clarify the imaging features of V180I gCJD, which would lead to prompt genetic counselling and analysis of the <i>PrP</i> gene, particularly focusing on cerebral cortex swelling. We included 35 patients with sCJD (<i>n</i> = 23) or V180I gCJD (<i>n</i> = 12). Cerebral cortex swelling on T2-weighted imaging (T2WI) or fluid-attenuated inversion recovery (FLAIR) wherein abnormal cortical hyperintensities were observed on DWI, and the distribution of grey matter hyperintensities on DWI were visually evaluated. V180I gCJD patients had significantly more cerebral cortex swelling (100% vs. 13.0%, <i>p</i> &lt; 0.001), an overall correct classification of 91.4%, and parahippocampal gyrus hyperintensities on DWI (100% vs. 39.1%, <i>q</i> = 0.019) than sCJD patients. Cerebral cortical hyperintensities on DWI with swelling on T2WI or FLAIR are characteristic imaging findings of V180I gCJD and are useful for differentiating it from sCJD.

日本最常见的遗传性克雅氏病（genetic Creutzfeldt-Jakob disease, gCJD）由朊蛋白（prion protein, PrP）基因180号密码子发生点突变所致，即缬氨酸被异亮氨酸取代（V180I gCJD）。现有研究证据表明，在弥散加权成像（diffusion-weighted imaging, DWI）上表现为异常高信号的大脑皮层肿胀，是V180I型遗传性克雅氏病的特征性磁共振成像（magnetic resonance imaging, MRI）表现。但目前尚无研究直接对比V180I gCJD与散发性克雅氏病（sporadic CJD, sCJD）的影像学特征。因此本研究旨在阐明V180I gCJD的影像学表现，以期为快速开展遗传咨询及朊蛋白基因分析提供依据，研究重点聚焦于大脑皮层肿胀。本研究共纳入35例患者，其中散发性克雅氏病患者23例、V180I gCJD患者12例。我们对两类患者中，弥散加权成像上存在皮层异常高信号者的T2加权成像（T2-weighted imaging, T2WI）或液体衰减反转恢复（fluid-attenuated inversion recovery, FLAIR）序列上的大脑皮层肿胀情况，以及弥散加权成像上灰质高信号的分布进行了视觉评估。与散发性克雅氏病患者相比，V180I gCJD患者的大脑皮层肿胀发生率显著更高（100% vs. 13.0%，p<0.001），整体分类准确率达91.4%，且弥散加权成像上海马旁回高信号的检出率也更高（100% vs. 39.1%，q=0.019）。弥散加权成像上的大脑皮层高信号伴T2WI或FLAIR序列上的皮层肿胀，是V180I gCJD的特征性影像学表现，可用于与散发性克雅氏病进行鉴别诊断。