视神经脊髓炎患者早期认知障碍的脑结构和功能基础及动态演变纵向研究

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are the most common inflammatory demyelinating diseases of the central nervous system (CNS), which are the major causes to disability in young adult after trauma. In non-white population including Chinese, NMO has high prevalence. Cognitive impairment can occur in early NMO and severely affects the life quality, however the neural basis and dynamic changes of the cognitive impairment of NMO is still unclear. In the current study, we plan to collect early NMO patients and healthy controls with detailed cognitive assessment and multi-modality MRI data to investigate the characteristics of cognitive impairment of early NMO patients, and explore the brain structural and functional changes including white matter lesions, white matter fiber integrity, grey matter atrophy and functional impairment/plasticity through routine MRI, high resolution structural MRI, diffusion tensor imaging (DTI) and resting-state fMRI. We try to demonstrate the neural basis of the cognitive impairment of early NMO and identify MRI biomarkers for early detection of cognitive impairment. In addition, we will follow up the patients and healthy controls for 3 years to observe the dynamic changes in both cognitive scores and MRI parameters, thus to investigate the predict values of the MRI biomarker which was identified at baseline. This project is essential to explore the possible neural basis of cognitive impairment in NMO and help identify early and objective biomarkers for early diagnosis and selecting optimal therapy, thus improve the patients’ life quality and alleviate the social and economic burden.

视神经脊髓炎（NMO）和多发性硬化是最常见的中枢神经系统脱髓鞘疾病，是中青年人群中非外伤性致残的最常见原因，其中NMO在非白种人包括中国人中尤为多见，NMO早期可出现认知障碍，严重影响患者生活，但对其认知障碍的神经机制和动态改变缺乏系统研究。本项目拟通过采集早期NMO患者和正常志愿者的临床认知评分和多模态MRI数据，尝试发现NMO早期认知障碍的特点，联合应用常规MRI序列（T2WI和FLAIR）、高分辨结构像、弥散张量成像、静息态功能磁共振从脑病灶、灰质萎缩、白质损伤和脑功能多个角度，并结合脑网络分析，探讨NMO认知障碍的脑结构和功能基础，筛选出能早期发现和客观评价NMO认知障碍的MRI标记物，并对患者的临床和影像学资料进行3年纵向随访，观察认知评分和脑连接的动态演变，尝试发现认知和脑连接改变的规律，验证横断面研究所发现的MRI标记物对于认知障碍发展的预测作用。

视神经脊髓炎（NMO）是非白种人包括中国人最常见的中枢神经系统脱髓鞘疾病，疾病早期可出现认知障碍，严重影响患者生活。本项目通过采集早期NMO患者和正常志愿者的临床认知评分和多模态MRI数据，联合应用常规MRI序列（T2WI和FLAIR）、高分辨结构像、弥散张量成像和静息态功能磁共振，分析了NMO患者脑结构和功能各项指标。研究发现NMO灰质萎缩和脑功能的损伤（低频振荡振幅、局部一致性、功能连接等指标异常）主要位于视觉、运动和认知相关的脑区，并且功能损伤和重塑并存。NMO灰质的结构改变与认知障碍相关，深部灰质尤其是海马、丘脑的萎缩是认知障碍的核心结构基础，提出脑结构和功能综合评价可以为认知障碍的预测提供客观指标。研究还发现NMO最早期临床孤立综合征（CIS）阶段脑功能连接和功能网络已经存在异常，并且脑功能网络的异常不受脑内病灶和脑体积变化的影响。创新性利用脑结构成像测算上颈段脊髓体积（MUCCA），发现NMO上颈段脊髓体积与患者临床残疾进展明显相关，可以用于临床试验影像学终点指标。依据本基金课题组发表6篇SCI文章（累计影响因子超过20分），另举办国内会议3次。在国际学术会议上做特邀报告3次。培养博士后1名，硕士研究生2名，执笔指南一部，主编书籍一本。