Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou City, 215004, China.
Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, China.
Ann Clin Transl Neurol. 2020 Oct;7(10):1930-1941. doi: 10.1002/acn3.51189. Epub 2020 Sep 15.
The rapidly increasing case reports revealed that neuronal intranuclear inclusion disease (NIID) had concomitant other system symptoms besides nervous system symptoms. In this study, we systematically evaluated the symptoms, signs, auxiliary examination, and pathological changes in different systems in NIID patients.
NIID patients were confirmed by examining GGC repeats in the NOTCH2NLC gene. Clinical data of NIID patients including symptoms, signs, and auxiliary examinations were collected for analysis. Ubiquitin and p62 were detected in different tissues from previous surgical samples.
Fifty-one NIID patients from 17 families were included in this study. Except neurological symptoms, clinical manifestations from other systems were very notable and diverse. The proportions of different system symptoms were 88.2% in nervous system, 78.4% in respiratory system, 72.5% in circulatory system, 72.5% in locomotor system, 66.7% in urinary system, 64.7% in digestive system, 61.5% in reproductive system, and 50.0% in endocrine system. In addition, other common symptoms included sexual dysfunction (43.1%), pupil constriction (56.9%), blurred vision (51.0%), and hearing loss (23.5%). Ubiquitin and p62-positive cells were found in different tissues and systems in 24 NIID patients with previous surgery. Initial symptoms of NIID and median onset age in different systems also revealed system heterogeneity of NIID.
For the first time, we systematically demonstrated that NIID is a heterogeneous and systemic neurodegenerative disease by providing clinical and pathological evidence. In addition to the nervous system, the clinical symptomatic and pathological spectrum of NIID has been extended to almost all systems.
不断增加的病例报告显示，神经元核内包涵体病（NIID）除神经系统症状外，还伴有其他系统症状。本研究系统评估了 NIID 患者不同系统的症状、体征、辅助检查和病理变化。
通过检测 NOTCH2NLC 基因中的 GGC 重复，确认 NIID 患者。收集 NIID 患者的临床资料，包括症状、体征和辅助检查进行分析。检测来自先前手术样本的不同组织中的泛素和 p62。
本研究纳入了 17 个家系的 51 例 NIID 患者。除神经症状外，其他系统的临床表现也非常显著和多样。不同系统症状的比例分别为神经系统 88.2%、呼吸系统 78.4%、循环系统 72.5%、运动系统 72.5%、泌尿系统 66.7%、消化系统 64.7%、生殖系统 61.5%和内分泌系统 50.0%。此外，其他常见症状包括性功能障碍（43.1%）、瞳孔缩小（56.9%）、视力模糊（51.0%）和听力损失（23.5%）。24 例有既往手术的 NIID 患者的不同组织和系统中发现了泛素和 p62 阳性细胞。不同系统的 NIID 首发症状和中位发病年龄也显示了 NIID 的系统异质性。
本研究首次提供了临床和病理证据，系统地证明了 NIID 是一种异质性和系统性神经退行性疾病。除了神经系统，NIID 的临床症状谱和病理谱已扩展到几乎所有系统。
