基因确诊的10例成人型神经元核内包涵体病患者的临床及影像学特点分析  

Clinical features and imaging manifestations in 10 patients with genetically diagnosed adult-onset neuronal intranuclear inclusion disease

作　　者：刘媛媛 靳玮 赵迪 臧卫周 张杰文 李书剑 Liu Yuanyuan;Jin Wei;Zhao Di;Zang Weizhou;Zhang Jiewen;Li Shujian(Department of Neurology,Henan Provincial People's Hospital,People's Hospital of Zhengzhou University,Zhengzhou 450003,China;Department of Ophthalmology,Henan Provincial People's Hospital,People's Hospital of Zhengzhou University,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院,郑州大学人民医院神经内科,郑州450003 [2]河南省人民医院,郑州大学人民医院眼科,郑州450003

出　　处：《中华神经医学杂志》2022年第7期664-670,共7页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金面上项目 (81873727)。

摘　　要：目的通过总结10例基因确诊的成人型神经元核内包涵体病(NIID)患者临床及影像学特点,为避免临床误诊提供依据。方法选择河南省人民医院神经内科自2020年1月至2022年3月诊治的10例NIID患者进入研究,所有患者均经NOTCH2NLC基因检测确诊。总结分析患者的临床资料、基因检测结果及皮肤组织病理结果。结果本组10例患者年龄为57~84岁,女性8例,男性2例。以发作性症状为主要表现者6例,其中3例表现为脑病,1例表现为短暂性全面性遗忘(TGA),1例表现为脑卒中样发作,1例表现为偏头痛;以慢性进展性症状为主要表现者4例,3例患者以痴呆为主,1例以帕金森综合征表现为主。DWI序列上双侧额叶皮髓交界处均出现特征性条带状高信号,T2 FLAIR序列上脑白质病变可早于DWI数年出现,病灶范围更广泛。10例患者均有NOTCH2NLC基因非编码区GGC重复突变且突变次数>60次。6例患者行皮肤活检,不同细胞内可见核内包涵体形成,免疫组化染色结果示泛素及p62阳性。结论NIID患者临床异质性大,以发作性症状为主要表现者多见,常合并慢性进展症状,其中脑卒中发作和偏头痛为NIID罕见的临床表型。头颅MRI DWI序列中皮髓交界区高信号是该病特征性影像学改变。Objective To summarize the clinical and imaging features of 10 patients with genetically diagnosed neuronal intranuclear inclusion disease(NIID)to avoid clinical misdiagnosis and mismanagement of NIID.Methods Ten patients with NIID,admitted to our hospital from January 2020 to March 2022,were chosen in our study.All patients were confirmed as having NIID by NOTCH2NLC gene assay.Their clinical data,gene detection results and skin pathological results were collected and anlyzed.Results These patients aged from 57 to 84 years,including 8 females.The episodic symptoms as main symptoms were noted in 6 patients,including 3 patients with encephalopathy,1 patient with TGA,1 patient with stroke-like episode,and 1 patient with migraine-like symptoms.Chronic progressive symptoms as main symptoms were noted in 4 patients,including 3 patients with dementia and 1 patient with Parkinson's disease.There were characteristic linear hyper-intensities in diffusion weighted imaging(DWI)in the corticomedullary junction predominantly in the frontal lobes.White matter lesions appeared in T2 Flair might have been noted years before lesions appeared in DWI,with wider ranges.All had GGC repeated expansion in NOTCH2NLC gene in non-coding area,with mutation number>60.Skin biopsy was performed in 6 patients,showing the formation of intranuclear inclusion bodies in different cells;and ubiquitin and P62 were found positive in immunohistochemical staining.Conclusions NIID patients have large clinical heterogeneity;most patients have episodic symptoms as main manifestations,often accompanied by chronic progressive symptoms;stroke attack and migraine are rare clinical phenotypes of NIID.The high signal at the cortical medullary junction in DWI is a characteristic imaging change.

关 键 词：神经元核内包涵体病 成人 NOTCH2NLC基因 发作性症状 

分 类 号：R741[医药卫生—神经病学与精神病学]