Advances of the pathological mechanism and related factors of cognitive impairment in neuromyelitis optica spectrum disorders
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摘要: 视神经脊髓炎谱系病(neuromyelitis optica spectrum disorders，NMOSD)是一种以单侧或双侧视神经炎、横贯性脊髓炎和脑干综合征为临床特征的中枢神经系统复发性自身免疫性炎症性疾病，水通道蛋白4抗体(aquaporin-4 immunoglobulin G antibody，AQP4-IgG)是其特异性致病抗体。长期以来，大量的研究已经证明多发性硬化(multiple sclerosis，MS)患者存在认知障碍，NMOSD认知障碍的问题以往因其神经生理残疾的情况更为突出而被忽视，先前的研究考虑NMOSD脑部的病灶导致包括认知障碍在内的临床残疾，近年来随着先进的神经影像学技术的应用和认知量表的测评，系列的研究已经证明有无脑部病灶的NMOSD患者均可能存在认知障碍，这揭示了疾病进程中可能存在的脑隐匿性病理损伤，考虑到疾病本身的高复发率和高致残率，NMOSD患者隐匿发展为合并认知障碍的情况将给患者本人和家庭带来严重的经济和精神负担，NMOSD认知障碍的问题逐渐引起临床和科研工作者的重视并取得进展，包括认知障碍神经影像学预测指标、病理学改变表现、血液分子指标等。本文回顾了NMOSD认知障碍的主要相关研究，系统阐述了NMOSD认知障碍的研究现状、病理学机制、认知量表、神经影像学进展以及其他因素对其认知的影响，为临床医生在日常工作中对评估NMOSD患者认知改变、疾病进展及治疗预后提供评估依据。Abstract: Neuromyelitis optica spectrum disorders (NMOSDs) are recurrent autoimmune inflammatory disorders of the central nervous system, with uni- or bilateral optic neuritis, transverse myelitis and brainstem syndromes as clinical hallmarks. Aquaporin-4 immunoglobulin G antibody (AQP4-IgG) is a specific pathogenic antibody to NMOSD. Numerous studies have demonstrated the presence of cognitive impairment in multiple sclerosis (MS) and the problem of cognitive impairment in NMOSD has previously been ignored because of its more prominent neurophysiological disability. In recent years, with the development of neuroimaging and measurement of cognitive scales, a series of studies has demonstrated that cognitive impairment may be present in NMOSD with or without brain lesions, thus revealing possible occult brain pathology damage in the disease process. Considering the high incidence rates of recurrence and disability, NMOSD insidiously progressing to comorbid cognitive impairment could bring serious economic and mental burdens to patients and families. The problem of cognitive impairment in NMOSD is gradually attracting the attention of clinical and scientific researchers and making progress, including neuroimaging predictors of cognitive impairment, neuropathological changes and molecular indicators of blood. In this article, the major studies on cognitive impairment in NMOSD are reviewed. The current status of research, pathological mechanisms, cognitive scales, neuroimaging advances and the effects of other factors of cognition in NMOSD is also systematically described, providing clinicians with a basis of assessing cognitive changes, disease progression and treatment prognosis in NMOSD in their clinical work.
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表 1 NMOSD认知障碍相关的主要研究
Table 1. Major studies related to cognitive impairment in NMOSD
参考文献 量表选择 认知障碍 BLANC F等(2008)[7] BCcogSEP(法译版BRN-B) 记忆，信息处理速度 CTT, Go-No-Go, WAIS-R 词语流畅性，执行能力 BDI HE D等(2011)[8] CVLT-Ⅱ, DST-backward 学习能力 CLOX, SDMT 记忆，信息处理速度 PASAT 3 s 词语流畅性，执行能力 BDI 执行能力 VANOTTI S等(2013)[11] MMSE 注意力，词语流畅性 BRB-N LIU Y O等(2015)[23] MACFIMS, WCST 词语流畅性，记忆 信息处理速度，执行能力 ZHANG N等(2015)[25] MMSE, MoCA 记忆，信息处理速度，执行能力 MACFIMS, WCST BDI KIM S H等(2016)[13] SVLT, HVLT-R, RCFT 记忆，注意力 COWAT, SDMT, PASAT 信息处理速度 DST, STROOP FUJIMORI J等(2017)[22] WAIS-Ⅲ，WMS-R 记忆，信息处理速度 WANG J等(2017)[18] mPASAT 注意力，记忆 LIU Y O等(2018)[4] MMSE 广泛认知 PASAT 信息处理速度 CHO E B等(2018)[32] DST, TMT, PASAT 注意力，工作记忆 DSCT, SST, K-BNT 信息处理速度，执行能力 RCFT, K-CVLT, COWAT 视空间能力 BDI-Ⅱ, STAI GUO X等(2019)[21] MMSE, MoCA, 广泛认知，记忆 CVLT-Ⅱ, BVMT-R, SDMT 视空间能力，信息处理速度 SAVOLDI F等(2019)[6] BRB-N 注意力，执行功能 STROOP 记忆 CHOU I J等(2019)[33] PASAT 3 s 运动功能，信息处理速度 FSS, T 25-FW, 9-HPT HAN Y L等(2019)[5] MMSE, MoCA 广泛认知 注：CTT，color trails test，色词测验；Go-No-Go，the go/no-go test，通过/不通过测试；WAIS-R，Wechsler memory scale-revised，韦克斯勒成人智力量表；BDI，the Beck depression inventory，贝克抑郁量表；CVLT-Ⅱ，California verbal learning test-Ⅱ，加利福尼亚词语学习测试-Ⅱ；DST-backward，the backward digit span test，后向数字跨度测试；CLOX，the executive clock drawing task，钟表绘制执行测验；SDMT，symbol digit modalities test，符号数字转换测验；PASAT 3 s，the Paced Auditory Serial Addition Test interstimulus time，3.0 s，进步式听觉累加测试，刺激时间3.0 s；WCST，Wisconsin card sorting test，威斯康星卡片分类测验；SVLT，Shiraz verbal learning test，Shiraz语言学习测验；RCFT，Rey complex figure test，Rey复杂图形测试；COWAT，controlled oral word association test，口语流畅性测验；STROOP，Stroop color-word test，Stroop色词测验(SCWT)；WMS-R，Wechsler memory scale-revised，韦克斯勒记忆量表修订版；mPASAT，modified PASAT，修改后的PASAT；TMT，trail making test，连线测验；DSCT，digit symbol coding test，数字符号编码测验；SST，spatial span test，空间跨度测试；K-BNT，Korean-Boston naming test，韩国版波士顿命名测试；STAI，state-trait anxiety inventory，状态特质焦虑量表；BVMT-R，the brief visuospatial memory test-revised，简短的视觉空间记忆测试修订；FSS，fatigue severity scale，疲劳强度量表；9-HPT，9-hole peg test，9孔钉测试；T 25-FW，timed 25-foot walk，定时25英尺步行。 
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