Neuronal intranuclear inclusion disease
10.3760/cma.j.cn113694-20240512-00336
- VernacularTitle:神经元核内包涵体病
- Author:
Zhaoxia WANG
1
;
Daojun HONG
Author Information
1. 北京大学第一医院神经内科，北京100034
- Publication Type:Journal Article
- Keywords:
Intranuclear inclusion bodies;
Neurons;
Ribbon sign;
NOTCH2NLC gene;
CGG repeat expansion
- From:
Chinese Journal of Neurology
2025;58(2):188-196
- CountryChina
- Language:Chinese
-
Abstract:
Neuronal intranuclear inclusion disease (NIID) is a genetic degenerative disease characterized by the presence of eosinophilic and p62-positive inclusions in the nucleus. The pathogenic variant is an abnormal CGG repeat expansion in the 5′ untranslated region of the NOTCH2NLC gene, leading to a pathogenesis of RNA toxicity and poly-glycine protein toxicity that impair cellular functions. NIID presents clinically with great heterogeneous phenotypes, comprising five subtypes: cognitive impairment predominance, movement disorder predominance, paroxysmal neurological events predominance, autonomic dysfunction predominance, and neuromuscular disease predominance. The magnetic resonance imaging (MRI) characteristics provide important diagnostic clues, including the "ribbon sign" at the corticomedullary junction on diffusion weighted imaging (DWI), diffuse white matter lesions symmetrically affecting the corona radiata and centrum semiovale, DWI hyperintensities in the splenium of the corpus callosum, and focal cortical edema with linear enhancement on the surface of corresponding cortex. With the applications of skin biopsies and genetic testing, an increasing number of NIID cases have been identified in China, resulting in recent advancements in clinical and basic research. This review highlights the pathogenesis, clinical manifestations, auxiliary examinations, differential diagnosis, and management of this disorder.
