在表现脑病样症状的神经元核内包涵体病中,"星形胶质细胞 "核内包涵体占优势:脑活检病例系列。

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY
Neuropathology Pub Date : 2024-10-01 Epub Date: 2024-03-13 DOI:10.1111/neup.12971
Keisuke Ishizawa, Takashi Komori, Taku Homma, Jun Sone, Yasuhiro Nakata, Yoshihiko Nakazato, Kazushi Takahashi, Toshimasa Yamamoto, Atsushi Sasaki
{"title":"在表现脑病样症状的神经元核内包涵体病中,\"星形胶质细胞 \"核内包涵体占优势:脑活检病例系列。","authors":"Keisuke Ishizawa, Takashi Komori, Taku Homma, Jun Sone, Yasuhiro Nakata, Yoshihiko Nakazato, Kazushi Takahashi, Toshimasa Yamamoto, Atsushi Sasaki","doi":"10.1111/neup.12971","DOIUrl":null,"url":null,"abstract":"<p><p>Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder represented by eosinophilic intranuclear inclusions (EIIs) and GGC/CGG repeat expansion in the NOTCH2NLC gene. We report here two adult cases of NIID, genetically confirmed, with manifestation of encephalopathy-like symptoms and address the histopathologic findings obtained by brain biopsies, with a focus on \"astrocytic\" intranuclear inclusions (AIIs). Case 1 presented with paroxysmal restlessness, vertigo, or fever and was later involved in severe dementia and tetraparesis. Case 2 presented with forgetfulness and then with paroxysmal fever and headache. In both cases, delimited areas with gadolinium enhancement on magnetic resonance imaging and corresponding hyperperfusion were detected, leading to brain biopsies of the cortex. On histology, Case 1 showed an abnormal lamination, where the thickness of layers was different from usual. Both neurons and astrocytes showed some dysmorphologic features. Notably, astrocytes rather than neurons harbored EIIs. Case 2 showed a cortex, where neurons tended to be arrayed in a columnar fashion. Astrocytes showed some dysmorphologic features. Notably, much more astrocytes than neurons harbored EIIs. By a double-labeling immunofluorescence study for p62/NeuN and p62/glial fibrillary acidic protein, the predominance of AIIs was confirmed in both cases. Considering the physiological functions of astrocytes for the development and maintenance of the cortex, the encephalopathy-like symptoms, dynamic change of cerebral blood flow, and cortical dysmorphology can reasonably be explained by the dysfunction of EII-bearing astrocytes rather than EII-bearing neurons. This study suggests the presence of a subtype of NIID where AIIs rather than \"neuronal\" intranuclear inclusions are likely a key player in the pathogenesis of NIID, particularly in cases with encephalopathy-like symptoms. The importance of AIIs (\"gliopathy\") should be more appreciated in future studies of NIID.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":" ","pages":"351-365"},"PeriodicalIF":1.3000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The predominance of \\\"astrocytic\\\" intranuclear inclusions in neuronal intranuclear inclusion disease manifesting encephalopathy-like symptoms: A case series with brain biopsy.\",\"authors\":\"Keisuke Ishizawa, Takashi Komori, Taku Homma, Jun Sone, Yasuhiro Nakata, Yoshihiko Nakazato, Kazushi Takahashi, Toshimasa Yamamoto, Atsushi Sasaki\",\"doi\":\"10.1111/neup.12971\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder represented by eosinophilic intranuclear inclusions (EIIs) and GGC/CGG repeat expansion in the NOTCH2NLC gene. We report here two adult cases of NIID, genetically confirmed, with manifestation of encephalopathy-like symptoms and address the histopathologic findings obtained by brain biopsies, with a focus on \\\"astrocytic\\\" intranuclear inclusions (AIIs). Case 1 presented with paroxysmal restlessness, vertigo, or fever and was later involved in severe dementia and tetraparesis. Case 2 presented with forgetfulness and then with paroxysmal fever and headache. In both cases, delimited areas with gadolinium enhancement on magnetic resonance imaging and corresponding hyperperfusion were detected, leading to brain biopsies of the cortex. On histology, Case 1 showed an abnormal lamination, where the thickness of layers was different from usual. Both neurons and astrocytes showed some dysmorphologic features. Notably, astrocytes rather than neurons harbored EIIs. Case 2 showed a cortex, where neurons tended to be arrayed in a columnar fashion. Astrocytes showed some dysmorphologic features. Notably, much more astrocytes than neurons harbored EIIs. By a double-labeling immunofluorescence study for p62/NeuN and p62/glial fibrillary acidic protein, the predominance of AIIs was confirmed in both cases. Considering the physiological functions of astrocytes for the development and maintenance of the cortex, the encephalopathy-like symptoms, dynamic change of cerebral blood flow, and cortical dysmorphology can reasonably be explained by the dysfunction of EII-bearing astrocytes rather than EII-bearing neurons. This study suggests the presence of a subtype of NIID where AIIs rather than \\\"neuronal\\\" intranuclear inclusions are likely a key player in the pathogenesis of NIID, particularly in cases with encephalopathy-like symptoms. The importance of AIIs (\\\"gliopathy\\\") should be more appreciated in future studies of NIID.</p>\",\"PeriodicalId\":19204,\"journal\":{\"name\":\"Neuropathology\",\"volume\":\" \",\"pages\":\"351-365\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/neup.12971\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/neup.12971","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/13 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

神经元核内包涵体病(NIID)是一种神经退行性疾病,表现为嗜酸性核内包涵体(EIIs)和NOTCH2NLC基因的GGC/CGG重复扩增。我们在此报告了两例经基因证实的 NIID 成人病例,他们均表现出类似脑病的症状,我们还讨论了脑活检获得的组织病理学结果,重点是 "星形胶质细胞 "核内包涵体(AIIs)。病例 1 表现为阵发性烦躁不安、眩晕或发热,后来出现严重痴呆和四肢瘫痪。病例 2 表现为健忘,随后出现阵发性发热和头痛。在这两个病例中,磁共振成像都发现了钆增强的分界区和相应的高灌注,因此对大脑皮层进行了活检。在组织学上,病例 1 显示出异常的分层,各层的厚度与平常不同。神经元和星形胶质细胞都表现出一些形态异常的特征。值得注意的是,星形胶质细胞而非神经元藏有 EII。病例 2 显示皮层中神经元呈柱状排列。星形胶质细胞表现出一些畸形特征。值得注意的是,星形胶质细胞比神经元携带更多的 EIIs。通过对 p62/NeuN 和 p62/胶质纤维酸性蛋白进行双重标记免疫荧光研究,证实了在这两种情况下 AIIs 占主导地位。考虑到星形胶质细胞对大脑皮层发育和维持的生理功能,脑病样症状、脑血流动态变化和大脑皮层畸形可以合理地解释为携带 EII 的星形胶质细胞功能障碍,而不是携带 EII 的神经元功能障碍。这项研究表明,在 NIID 亚型中,核内包涵体(AIIs)而非 "神经元 "核内包涵体可能是 NIID 发病机制中的关键因素,尤其是在出现脑病样症状的病例中。在今后的 NIID 研究中,应更加重视 AIIs("神经胶质病变")的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The predominance of "astrocytic" intranuclear inclusions in neuronal intranuclear inclusion disease manifesting encephalopathy-like symptoms: A case series with brain biopsy.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder represented by eosinophilic intranuclear inclusions (EIIs) and GGC/CGG repeat expansion in the NOTCH2NLC gene. We report here two adult cases of NIID, genetically confirmed, with manifestation of encephalopathy-like symptoms and address the histopathologic findings obtained by brain biopsies, with a focus on "astrocytic" intranuclear inclusions (AIIs). Case 1 presented with paroxysmal restlessness, vertigo, or fever and was later involved in severe dementia and tetraparesis. Case 2 presented with forgetfulness and then with paroxysmal fever and headache. In both cases, delimited areas with gadolinium enhancement on magnetic resonance imaging and corresponding hyperperfusion were detected, leading to brain biopsies of the cortex. On histology, Case 1 showed an abnormal lamination, where the thickness of layers was different from usual. Both neurons and astrocytes showed some dysmorphologic features. Notably, astrocytes rather than neurons harbored EIIs. Case 2 showed a cortex, where neurons tended to be arrayed in a columnar fashion. Astrocytes showed some dysmorphologic features. Notably, much more astrocytes than neurons harbored EIIs. By a double-labeling immunofluorescence study for p62/NeuN and p62/glial fibrillary acidic protein, the predominance of AIIs was confirmed in both cases. Considering the physiological functions of astrocytes for the development and maintenance of the cortex, the encephalopathy-like symptoms, dynamic change of cerebral blood flow, and cortical dysmorphology can reasonably be explained by the dysfunction of EII-bearing astrocytes rather than EII-bearing neurons. This study suggests the presence of a subtype of NIID where AIIs rather than "neuronal" intranuclear inclusions are likely a key player in the pathogenesis of NIID, particularly in cases with encephalopathy-like symptoms. The importance of AIIs ("gliopathy") should be more appreciated in future studies of NIID.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信