临床孤立综合征患者脊髓功能损伤和重塑的评价和转归预测研究

A clinically isolated syndrome (CIS) is defined as an episode suggestive of central nervous system inflammatory demyelination, which is the first clinical event for several demyelinating diseases such as multiple sclerosis or neuromyelitis optica spectrum disorder. Most of the previous studies were focused on brain structural and functional changes in CIS, however spinal cord changes are essential contributor for CIS conversion or clinical disability progression. A systematic study of spinal cord especially functional alterations of spinal cord is warranted to explore the potential mechanisms and identify biomarkers. In the current study, we plan to collect CIS patients and healthy controls with detailed clinical assessment and multi-modality spinal cord MRI data particularly task-related and resting-state fMRI to investigate the spinal cord functional impairment and plasticity of CIS patients, and explore the spinal cord structural changes including lesions, spinal cord volume and white matter fiber integrity through routine MRI, high resolution structural MRI, diffusion tensor imaging (DTI). We try to demonstrate the neural basis of the spinal cord functional changes in CIS and identify the association between spinal cord fMRI alterations and clinical scores. In addition, we will follow up the patients and healthy controls for 3 years to observe the dynamic changes in both clinical scores and MRI parameters, thus to investigate the clinical values of the MRI biomarkers for predicting the clinical conversion and disability progression. This project is essential to explore spinal cord functional changes in CIS 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.

临床孤立综合征(clinically isolated syndrome,CIS)是中枢神经脱髓鞘疾病的首次发作，具有多种转归，其预后和最佳治疗存在显著差异，早期发现CIS的结构和功能改变，预测CIS的转归和残疾程度进展具有重大的科学和临床意义。既往研究主要集中在CIS的脑改变，对其脊髓尤其是脊髓功能改变及其科学和临床价值缺乏系统研究。本研究拟通过采集CIS脊髓任务相关和静息态功能MRI，全面评价CIS脊髓的早期功能损伤和重塑，并联合结构MRI（高分辨结构像、弥散成像）评价脊髓的结构损伤，全面探讨CIS脊髓功能损伤和重塑的结构基础，以及功能损伤和重塑和临床残疾程度的关系，对患者进行3年临床和影像随访，观察脊髓功能损伤和重塑的演变规律，验证横断面研究所发现的影像学标记物对于CIS临床转归和残疾程度进展的预测作用，联合临床指标建立CIS转归的预测模型，指导早期精准治疗和判断预后。

临床孤立综合征(clinically isolated syndrome, CIS)是中枢神经脱髓鞘疾病的首次发作，具有多种转归，其预后和最佳治疗存在显著差异。早期发现CIS的结构和功能改变，预测CIS的转归和残疾程度进展具有重大的科学和临床意义。既往研究主要集中在CIS的脑改变，对其脊髓尤其是脊髓功能改变及其科学和临床价值缺乏系统研究。.本项目基于MRI结构像及功能MRI，对CIS等神经免疫疾病患者脊髓和脑内的病灶、结构损伤、以及功能损伤和重塑的情况进行了系统评价；发现了患者脊髓功能损伤和重塑的结构基础，揭示了各神经免疫疾病间结构和功能损伤及重塑的异质性。在此基础上，通过对患者进行1-3年临床和影像随访，明确脊髓和脑结构和功能综合评价可以为临床残疾程度的预测提供客观指标，指导早期精准治疗和判断预后。本研究丰富了中枢神经系统脱髓鞘疾病的学科内涵，为疾病的早起诊断和精准诊疗做出贡献。. 本研究确立了脊髓规范化扫描的MRI流程及参数，构建了神经免疫疾病脊髓影像评价的体系，建立了神经系统炎性及肿瘤性疾病脊髓和脑内病灶分割模型，脊髓疾病鉴别诊断模型、脑龄预测模型，为神经系统脊髓病变评估的规范化、统一化提供了策略，具有十分重要的应用前景。. 依据本基金课题组发表15篇SCI文章，举办多次国内会议，培养博士后1名，博士研究生3名，硕士研究生6名，获得国家发明专利2项，参于制定指南2部。