Neuronal intranuclear inclusion disease with subtle imaging findings: a case report and literature review

Introduction Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Hyperintense signals on diffusion-weighted imaging (DWI) at the corticomedullary junction are key diagnostic features. Early manifestations are often overlooked, leading to misdiagnoses. Here, we report...

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Main Authors: Tian Zhang, Xiaoying Zhang, Jiehua Ma, Ziyang Huang, Yuwen Wang, Meiduo Gesang, Chenling Hu
Format: Article
Language:English
Published: BMJ Publishing Group 2025-08-01
Series:BMJ Neurology Open
Online Access:https://neurologyopen.bmj.com/content/7/2/e001033.full
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author Tian Zhang
Xiaoying Zhang
Jiehua Ma
Ziyang Huang
Yuwen Wang
Meiduo Gesang
Chenling Hu
author_facet Tian Zhang
Xiaoying Zhang
Jiehua Ma
Ziyang Huang
Yuwen Wang
Meiduo Gesang
Chenling Hu
author_sort Tian Zhang
collection DOAJ
description Introduction Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Hyperintense signals on diffusion-weighted imaging (DWI) at the corticomedullary junction are key diagnostic features. Early manifestations are often overlooked, leading to misdiagnoses. Here, we report a case of adult-onset NIID with DWI hyperintensities at the corticomedullary junction.Case presentation A 72-year-old woman presented with progressive memory deterioration starting 9 years ago. In the third year, MRI showed extensive white matter lesions and brain atrophy, with focal high signal intensity in the corticomedullary junction of the frontal lobe; however, this was overlooked. The patient was clinically diagnosed with Alzheimer’s disease. In the seventh year, the patient gradually developed emotional instability, bradykinesia and urinary incontinence. In the eighth year, MRI revealed a remarkable curvilinear DWI hyperintense signal at the corticomedullary junction. Further genetic testing identified 105 GGC repeats in the NOTCH2NLC gene. Skin biopsy revealed intranuclear inclusions in P62 and ubiquitin-positive fibroblasts, confirming the NIID diagnosis.Conclusions Patients with NIID show characteristic DWI hyperintensity at the corticomedullary junction during symptoms. This early imaging finding is subtle and often overlooked. For patients with dementia and episodic encephalopathy, observing radiological changes, along with genetic and skin biopsies, is indispensable.
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spelling doaj-art-351e2910883f4df68947c9d06ce4c90a2025-08-20T03:03:45ZengBMJ Publishing GroupBMJ Neurology Open2632-61402025-08-017210.1136/bmjno-2025-001033Neuronal intranuclear inclusion disease with subtle imaging findings: a case report and literature reviewTian Zhang0Xiaoying Zhang1Jiehua Ma2Ziyang Huang3Yuwen Wang4Meiduo Gesang5Chenling Hu61Xencor Inc., Pasadena, CA, USA1 Department of Rheumatology and Immunology, Peking University People`s Hospital, Beijing, ChinaNanjing Maternal and Child Health Institute;Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, 300060, ChinaZhejiang University School of Medicine Affiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Hangzhou, ChinaZhejiang University School of Medicine Affiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Hangzhou, ChinaIntroduction Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Hyperintense signals on diffusion-weighted imaging (DWI) at the corticomedullary junction are key diagnostic features. Early manifestations are often overlooked, leading to misdiagnoses. Here, we report a case of adult-onset NIID with DWI hyperintensities at the corticomedullary junction.Case presentation A 72-year-old woman presented with progressive memory deterioration starting 9 years ago. In the third year, MRI showed extensive white matter lesions and brain atrophy, with focal high signal intensity in the corticomedullary junction of the frontal lobe; however, this was overlooked. The patient was clinically diagnosed with Alzheimer’s disease. In the seventh year, the patient gradually developed emotional instability, bradykinesia and urinary incontinence. In the eighth year, MRI revealed a remarkable curvilinear DWI hyperintense signal at the corticomedullary junction. Further genetic testing identified 105 GGC repeats in the NOTCH2NLC gene. Skin biopsy revealed intranuclear inclusions in P62 and ubiquitin-positive fibroblasts, confirming the NIID diagnosis.Conclusions Patients with NIID show characteristic DWI hyperintensity at the corticomedullary junction during symptoms. This early imaging finding is subtle and often overlooked. For patients with dementia and episodic encephalopathy, observing radiological changes, along with genetic and skin biopsies, is indispensable.https://neurologyopen.bmj.com/content/7/2/e001033.full
spellingShingle Tian Zhang
Xiaoying Zhang
Jiehua Ma
Ziyang Huang
Yuwen Wang
Meiduo Gesang
Chenling Hu
Neuronal intranuclear inclusion disease with subtle imaging findings: a case report and literature review
BMJ Neurology Open
title Neuronal intranuclear inclusion disease with subtle imaging findings: a case report and literature review
title_full Neuronal intranuclear inclusion disease with subtle imaging findings: a case report and literature review
title_fullStr Neuronal intranuclear inclusion disease with subtle imaging findings: a case report and literature review
title_full_unstemmed Neuronal intranuclear inclusion disease with subtle imaging findings: a case report and literature review
title_short Neuronal intranuclear inclusion disease with subtle imaging findings: a case report and literature review
title_sort neuronal intranuclear inclusion disease with subtle imaging findings a case report and literature review
url https://neurologyopen.bmj.com/content/7/2/e001033.full
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