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Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improv...

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Autores principales: Zhao, Bo, Yang, Miao, Wang, Zhiwei, Yang, Qiqiong, Zhang, Yimo, Qi, Xiaokun, Pan, Shuyi, Yu, Yingxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762495/
https://www.ncbi.nlm.nih.gov/pubmed/36545534
http://dx.doi.org/10.3389/fnins.2022.1056261
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author Zhao, Bo
Yang, Miao
Wang, Zhiwei
Yang, Qiqiong
Zhang, Yimo
Qi, Xiaokun
Pan, Shuyi
Yu, Yingxin
author_facet Zhao, Bo
Yang, Miao
Wang, Zhiwei
Yang, Qiqiong
Zhang, Yimo
Qi, Xiaokun
Pan, Shuyi
Yu, Yingxin
author_sort Zhao, Bo
collection PubMed
description BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID. MATERIALS AND METHODS: We presented two cases of NIID diagnosed by using NOTCH2NLC gene testing and skin biopsy. Diffusion weighted imaging (DWI) showed high linear intensity in corticomedullary junction. We also reviewed all the published NIID cases with positive NOTCH2NLC GGC repeat expansion and skin biopsy results in PubMed. RESULTS: Patient 1 was a 63-year-old male who carried 148 GGC repeats and presented with progressive tremor and limb weakness. Patient 2 was a 62-year-old woman who carried 131 GGC repeats and presented with tremors, memory loss and headaches. The most common clinical manifestation of 63 NIID patients in this study was cognitive impairment, followed by tremors. In our study, almost all the patients were from East Asia, the male to female ratio was 1:1.26, with an age of onset of 54.12 ± 14.12 years, and an age of diagnosis of 60.03 ± 12.21 years. Symmetrical high signal intensity at the corticomedullary junction on DWI were revealed in 80.96% of the patients. For the GGC repeat numbers, the majority of GGC repeats were in the 80–119 intervals, with few GGC repeats above 160. The number of GGC repetitions was significantly higher in patients presented with muscle weakness than in other clinical manifestations. CONCLUSION: NIID is a neurodegenerative disease caused by aberrant polyglycine (polyG) protein aggregation. NIID mostly occurs in the elderly population in East Asia, with cognitive dysfunction as the most common symptom. Staging NIID based on clinical presentation is inappropriate because most patients with NIID have overlapping symptoms. In our study, there was no significant correlation between the number of GGC repeats and different phenotypes except for muscle weakness. Abnormal trinucleotides repeat and PolyG protein aggregation maybe common pathogenic mechanism in neurodegenerative diseases and cerebrovascular diseases, which needs to be confirmed by more studies.
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spelling pubmed-97624952022-12-20 Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review Zhao, Bo Yang, Miao Wang, Zhiwei Yang, Qiqiong Zhang, Yimo Qi, Xiaokun Pan, Shuyi Yu, Yingxin Front Neurosci Neuroscience BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID. MATERIALS AND METHODS: We presented two cases of NIID diagnosed by using NOTCH2NLC gene testing and skin biopsy. Diffusion weighted imaging (DWI) showed high linear intensity in corticomedullary junction. We also reviewed all the published NIID cases with positive NOTCH2NLC GGC repeat expansion and skin biopsy results in PubMed. RESULTS: Patient 1 was a 63-year-old male who carried 148 GGC repeats and presented with progressive tremor and limb weakness. Patient 2 was a 62-year-old woman who carried 131 GGC repeats and presented with tremors, memory loss and headaches. The most common clinical manifestation of 63 NIID patients in this study was cognitive impairment, followed by tremors. In our study, almost all the patients were from East Asia, the male to female ratio was 1:1.26, with an age of onset of 54.12 ± 14.12 years, and an age of diagnosis of 60.03 ± 12.21 years. Symmetrical high signal intensity at the corticomedullary junction on DWI were revealed in 80.96% of the patients. For the GGC repeat numbers, the majority of GGC repeats were in the 80–119 intervals, with few GGC repeats above 160. The number of GGC repetitions was significantly higher in patients presented with muscle weakness than in other clinical manifestations. CONCLUSION: NIID is a neurodegenerative disease caused by aberrant polyglycine (polyG) protein aggregation. NIID mostly occurs in the elderly population in East Asia, with cognitive dysfunction as the most common symptom. Staging NIID based on clinical presentation is inappropriate because most patients with NIID have overlapping symptoms. In our study, there was no significant correlation between the number of GGC repeats and different phenotypes except for muscle weakness. Abnormal trinucleotides repeat and PolyG protein aggregation maybe common pathogenic mechanism in neurodegenerative diseases and cerebrovascular diseases, which needs to be confirmed by more studies. Frontiers Media S.A. 2022-12-05 /pmc/articles/PMC9762495/ /pubmed/36545534 http://dx.doi.org/10.3389/fnins.2022.1056261 Text en Copyright © 2022 Zhao, Yang, Wang, Yang, Zhang, Qi, Pan and Yu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Zhao, Bo
Yang, Miao
Wang, Zhiwei
Yang, Qiqiong
Zhang, Yimo
Qi, Xiaokun
Pan, Shuyi
Yu, Yingxin
Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review
title Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review
title_full Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review
title_fullStr Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review
title_full_unstemmed Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review
title_short Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review
title_sort clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762495/
https://www.ncbi.nlm.nih.gov/pubmed/36545534
http://dx.doi.org/10.3389/fnins.2022.1056261
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