Clinical Features and Classification of Neuronal Intranuclear Inclusion Disease

作者：Hongfei Tai, An Wang, Yumei Zhang, Shaocheng Liu, Yunzhu Pan, Kai Li, Gui‐Xian Zhao, Mengwen Wang, Guode Wu, Songtao Niu, Hua Pan, Bin Chen, Wei Li, Xingao Wang, Gehong Dong, Wei Li, Ying Zhang, Sheng Guo, Xiaoyun Liu, Mingxia Li, Hui Liang, Ming Huang, W. Chen, Zaiqiang Zhang · 发表于：Neurology Genetics · 年份：2023 · DOI：10.1212/nxg.0000000000200057 · 被引用次数：81 · 研究领域：Genetic Neurodegenerative Diseases、Neurological diseases and metabolism、Mitochondrial Function and Pathology

Background and Objectives Neuronal intranuclear inclusion body disease (NIID) is a neurodegenerative disease with highly heterogeneous clinical manifestations. The present study aimed to characterize clinical features and propose a classification system based on a large cohort of NIID in China. Methods The Chinese NIID registry was launched from 2017, and participants9 demographics and clinical features were recorded. Brain MRI, skin pathologies, and the number of GGC repeat expansions in the 5′ untranslated region of the NOTCH2NLC gene were evaluated in all patients. Results In total, 223 patients (64.6% female) were recruited; the mean (SD) onset age was 56.7 (10.3) years. The most common manifestations were cognitive impairment (78.5%) and autonomic dysfunction (70.9%), followed by episodic symptoms (51.1%), movement disorders (50.7%), and muscle weakness (25.6%). Imaging markers included hyperintensity signals along the corticomedullary junction on diffusion-weighted imaging (96.6%), white matter lesions (98.1%), paravermis (55.0%), and focal cortical lesions (10.1%). The median size of the expanded GGC repeats in these patients was 115 (range, 70–525), with 2 patients carrying >300 GGC repeats. A larger number of GGC repeats was associated with younger age at onset ( r = −0.329, p < 0.0001). According to the proposed clinical classification based on the most prominent manifestations, the patients were designated into 5 distinct types: cognitive impairment...