Neuronal Intranuclear Inclusion Disease

HomeRadiologyVol. 316, No. 3 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyNeuronal Intranuclear Inclusion DiseaseXiaoyu Liu1, Binglin Lai1 Xiaoyu Liu1, Binglin Lai1 Author Affiliations1Ganzhou Institute of Medical Imaging, Ganzhou Key Laboratory of Medical Imaging and Artificial Intelligence, Medical Imaging Center, Ganzhou People's Hospital, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, 16 Meiguan Ave, Ganzhou 341000, PR ChinaAddress correspondence to: B.L. (email: [email protected]).Xiaoyu Liu1Binglin Lai1 Published Online:Sep 2 2025https://doi.org/10.1148/radiol.243534MoreSectionsPDF ToolsAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookXLinked In A 58-year-old woman presented with a 1-year history of progressive cognitive decline, including memory impairment, forgetfulness, and an inability to recognize family members. Brain MRI (Fig 1) revealed diffuse symmetrical white matter lesions involving the corpus callosum. Diffusion-weighted images showed symmetrical strip-like and gyriform high-signal-intensity alterations in the gray-white matter junction of the bilateral frontal, temporal, and parietal lobes, resembling the previously reported "cockscomb sign" (1). These MRI characteristics were deemed suggestive of neuronal intranuclear inclusion disease (NIID). The diagnosis was confirmed with skin biopsy (Fig 2) and dynamic mutation testing of the NOTCH2NLC gene.Figure 1: Imaging findings in a 58-year-old woman with cognitive decline due to neuronal intranuclear inclusion disease. (A) T2-weighted and (B) fluid-attenuated inversion recovery, or FLAIR, MRI scans reveal bilateral diffuse symmetrical hyperintensities in the white matter. (C, D) Diffusion-weighted images (b value = 1000 sec/mm2) show symmetrical strip-like and gyriform high-signal-intensity alterations in the gray-white matter junction of the bilateral frontal and parietal lobes involving the corpus callosum, which resemble the "cockscomb sign." (E, F) Apparent diffusion coefficient images reveal corresponding hyperintense signal alterations at the corticomedullar junction, whereas the lesions in the corpus callosum appear hypointense. C and E show the corpus callosum, while D and F show the parietal lobes.Figure 1:Download as PowerPointFigure 2: Electron microscopy image of a specimen obtained at skin biopsy depicts a characteristic intranuclear inclusion body (arrow). Intranuclear inclusion bodies are typically round with clear borders and composed of fine fibrillary material. Scale bar = 1 μm. (Photomicrograph courtesy of Jianfeng Huang, MD, Guangzhou KingMed Center for Clinical Laboratory.)Figure 2:Download as PowerPoint NIID is a rare, chronic, progressive neurodegenerative disorder characterized by the formation of eosinophilic, transparent inclusions within the nuclei of neurons in the central and peripheral nervous systems. The classification of NIID comprises five clinical categories based on dominant clinical features, including the cognitive impairment–dominant type, the movement disorder–dominant type, the episodic neurogenic event–dominant type, the autonomic dysfunction–dominant type, and the neuromuscular disease–dominant type (2). MRI findings of adult-onset NIID such as those presented here include hyperintense signal alterations in the subcortical region on diffusion-weighted images. Additional features include bilateral, diffuse, symmetrical white matter hyperintensities on T2-weighted and fluid-attenuated inversion recovery, or FLAIR, images, as well as high signal intensity in the splenium of the corpus callosum on diffusion-weighted images. Currently, there is no specific treatment for NIID, and management is focused on symptomatic support.Disclosures of conflicts of interest: X.L. No relevant relationships. B.L. No relevant relationships.Acknowledgments We are grateful for the assistance provided by Jianhua Yang, MD, and Yuping Zeng, MD, as well as Jianfeng Huang, MD, from Guangzhou KingMed Center for Clinical Laboratory for providing and agreeing to the use of the electron microscope image. Funding: Supported by the Clinical Research Center for Medical Imaging in Jiangxi Province (grant no. 20223BCG7400199). Data sharing: Data generated or analyzed during the study are available from the corresponding author by request.References1. Zhang Z, Xu Q, Li J, et al. MRI features of neuronal intranuclear inclusion disease, combining visual and quantitative imaging investigations. J Neuroradiol 2024;51(3):274–280. Medline Google Scholar2. Tai H, Wang A, Zhang Y, et al; China NIID Collaboration Alliance. Clinical Features and Classification of Neuronal Intranuclear Inclusion Disease. Neurol Genet 2023;9(2):e200057. Medline Google ScholarArticle HistoryReceived: Nov 20 2024Revision requested: Jan 17 2025Revision received: Feb 25 2025Accepted: June 23 2025Published online: Sept 02 2025 FiguresReferencesRelatedDetails Vol. 316, No. 3 Metrics Altmetric Score PDF download