【作者】 刘佳；

【导师】 李静；

【作者基本信息】 中南大学 ， 临床医学（专业学位）， 2024， 硕士

【摘要】 研究背景:多发性硬化(multiple sclerosis,MS)是一种罕见的免疫介导的慢性中枢神经系统(central nervous system,CNS)炎症性疾病,由于视觉传导通路是MS最常受累的白质通路之一,因此大多数MS患者在疾病的整个发展进程中都会出现视觉传导通路损害,进而导致视觉障碍。视觉通路损害提示急性视神经炎和视网膜周围炎造成的急性局灶性CNS损害,以及通过慢性视网膜病变和视神经病变造成的慢性弥漫性CNS损害。研究表明MS患者因视觉障碍导致生活质量显著降低,深入研究MS患者视觉障碍损害的结构及功能特征,明确MS视觉通路损害的潜在影像学特征,积极预防并提前干预视觉传导通路损害,将为MS患者视觉损害防治提供新的切入点。研究目的:本研究基于静息态功能MRI(resting state functional MRI,rs-f MRI)和光学相干断层扫描(optical coherence tomography,OCT)/光学相干断层扫描血管造影(optical coherence tomography angiography,OCTA)等影像学研究方法,着眼于复发-缓解型MS(relapsing-remitting MS,RRMS)患者的视觉通路,通过研究视觉通路结构变化及rs-f MRI的影像学改变,以探索论证MS视觉通路损害的潜在致病机制。研究方法:招募2021年9月至2023年11月在中南大学湘雅医院就诊的RRMS患者39例,39例患者均完成rs-f MRI检查,同时招募15名健康对照(healthy controls,HCs)完成rs-f MRI检查;39例RRMS中有19例在rs-MRI检查完成后2周内完善了OCT/OCTA检查,另外匹配19名完成OCT/OCTA检查的HCs,使用符号数字模拟测验(symbol digit modalities test,SDMT)量表评估受试者的认知功能。进行RRMS和HCs临床特征、局部一致性(regional homogeneity,Re Ho)、体素镜像同伦连接(voxel-mirrored homotopic connectivity,VMHC)分析、功能连接(functional connectivity,FC)分析以及黄斑视网膜厚度、视乳头周围视网膜神经纤维层厚度(peripapillary retinal nerve fiber layer,p RNFL)、黄斑视网膜浅层血管密度和血流灌注密度的定量分析,将上述研究结果与临床特征、SDMT评分进行相关性分析。研究结果:1.与HCs相比,RRMS患者存在枕叶视觉区左侧枕中回Re Ho值明显降低(体素水平P<0.01,簇水平P<0.05,簇大小>153)。2.与HCs相比,RRMS患者存在枕叶双侧距状裂周围皮层VMHC值明显降低(体素水平P<0.01,簇水平P<0.05,簇大小>96)。3.选择以左侧枕中回和右侧距状裂周围皮层作为感兴趣的种子点进行FC分析,评估其他脑区与种子点之间的功能连接关系,结果经组内及组间比较校正后差异均无统计学意义(P>0.05)。4.与HCs相比,RRMS患者黄斑视网膜平均厚度显著变薄(P<0.05)。将黄斑视网膜根据早期糖尿病视网膜病变研究(ETDRS)分区后,结果显示,除中心区外,中上、中鼻、中下、中颞、外上、外鼻、外下、外颞区的视网膜厚度均显著低于HCs组(P<0.05);同时RRMS患者视乳头p RNFL厚度明显低于HCs(P<0.05),将视乳头p RNFL划分为12个钟点后,结果发现2点、3点、6点、8点、9点、10点、12点位的的p RNFL厚度在2组之间差异具有统计学意义(P<0.05)。5.RRMS患者的平均p RNFL厚度和发病次数存在显著的负相关关系(P<0.05,r=-0.474),与SDMT评分之间存在显著的正相关关系(P<0.05,r=0.515)。6.RRMS和HCs两组间OCTA的结果相似,RRMS患者仅有外下区浅层血管密度低于HCs组(P<0.05),以及在外下区和外颞区的血流灌注密度低于HCs组(P<0.05)。7.RRMS患者的视盘面积有减少的趋势,但与HCs比较差异无统计学意义(P>0.05);2组间黄斑中心凹无血管区(foveal avascular zone,FAZ)面积和FAZ周长差异均无统计学意义(P>0.05)。研究结论:1.RRMS患者的视觉区存在神经元同步性活动紊乱,双侧枕叶视觉区之间的功能连接程度受损以及视觉产生功能过程的协同性变差。2.RRMS患者前视通路视网膜层厚度变薄、血管密度和血流灌注密度减少,后视通路的神经元功能一致性和视觉网络受损。双向跨突触变性可能是RRMS患者视觉通路损害的潜在致病机制。图19幅,表10个,参考文献75篇更多还原

【Abstract】 Background:Multiple sclerosis(MS)is a rare immune-mediated chronic inflammatory disease of the central nervous system(CNS).Since the visual pathway is one of the most commonly affected white matter pathways in MS,most MS patients experience visual pathway damage throughout the course of the disease,leading to visual impairment.Visual pathway damage suggests acute focal CNS damage caused by acute optic neuritis and perioptic neuritis,as well as chronic diffuse CNS damage caused by chronic retinal and optic nerve lesions.Studies have shown that visual impairment significantly reduces the quality of life in MS patients.In-depth research on the structural and functional characteristics of visual impairment in MS patients,clarification of the potential imaging features of MS visual pathway damage,active prevention,and early intervention of visual pathway damage will provide new insights into the prevention and treatment of visual impairment in MS patients.Objective:Based on imaging research methods such as resting-state functional MRI(rs-f MRI)and optical coherence tomography(OCT)/optical coherence tomography angiography(OCTA),this study focuses on the visual pathway of patients with relapsing-remitting MS(RRMS).By studying the structural changes of the visual pathway and imaging changes of rs-f MRI,we aim to explore and demonstrate the potential pathogenic mechanisms of visual pathway damage in MS.Methods:We recruited 39 patients with RRMS who were treated at Xiangya Hospital,Central South University,from September 2021 to November 2023,and 15 healthy controls(HCs)to undergo rs-f MRI examinations together.All 39 RRMS patients completed rs-f MRI scans,and underwent rs-f MRI scans together with 15 healthy controls(HCs)as a control group.Additionally,19 of the RRMS patients completed OCT and OCTA examinations within 2 weeks.The Symbol Digit Modalities Test(SDMT)was used to assess the cognitive function of the participants.Clinical characteristics,regional homogeneity(Re Ho),voxel-mirrored homotopic connectivity(VMHC)analysis,functional connectivity(FC)analysis,as well as quantitative analysis of macular retinal thickness,peripapillary retinal nerve fiber layer thickness(p RNFL),macular retinal superficial vascular density,and blood perfusion density were performed in RRMS and HCs.The correlation between the above research results,clinical characteristics,and SDMT scores was analyzed.Results:1.Compared to HCs,RRMS patients exhibited significantly decreased Re Ho values in the left cuneus visual area(voxel-level P<0.01,cluster-level P<0.05,cluster size>153).2.RRMS patients showed significantly reduced VMHC values around the bilateral cuneus(voxel-level P<0.01,cluster-level P<0.05,cluster size>96)compared to HCs.3.Functional connectivity analysis using the left posterior cingulate gyrus and the cortical areas surrounding the right fissure of Sylvius as seed points showed no significant differences in within-group and between-group comparisons(P>0.05).4.Compared with HCs,patients with RRMS had significantly thinner macular retinal average thickness(P<0.05).After dividing the macular retina according to the Early Treatment Diabetic Retinopathy Study(ETDRS)subfields,the results showed that,except for the central subfield,the retinal thickness in the superior inner,nasal inner,inferior inner,temporal inner,superior outer,nasal outer,inferior outer,and temporal outer subfields were significantly lower in the RRMS group than in the HCs group(P<0.05).Additionally,the peripapillary retinal nerve fiber layer(p RNFL)thickness was significantly lower in patients with RRMS compared to HCs(P<0.05).After dividing the p RNFL into 12clock-hour sectors,statistical differences in p RNFL thickness between the two groups were found at the 2 o’clock,3 o’clock,6 o’clock,8 o’clock,9o’clock,10 o’clock,and 12 o’clock positions(P<0.05).5.There was a significant negative correlation between the average p RNFL thickness and the number of relapses in patients with RRMS(P<0.05,r=-0.474),and a significant positive correlation was observed between the p RNFL thickness and SDMT scores(P<0.05,r=0.515).6.OCTA results were similar between the RRMS and HCs groups.Patients with RRMS only showed lower superficial vascular density in the inferior outer subfield compared to the HCs group(P<0.05),as well as lower blood perfusion density in the inferior outer and temporal outer subfields compared to the HCs group(P<0.05).7.There was a decreasing trend in the optic disc area in patients with RRMS,but it was not statistically significant compared to HCs(P>0.05).There were also no statistically significant differences in the foveal avascular zone(FAZ)area and FAZ perimeter between the two groups(P>0.05).Conclusion:1.RRMS patients exhibit disrupted neuronal synchrony activity in the visual area,with impaired functional connectivity between bilateral cuneus visual areas and decreased coordination in visual processing.2.In patients with RRMS,thinning of the retinal layers in the anterior visual pathway,along with reduced vascular density and perfusion density,as well as impaired neuronal functional coherence in the posterior visual pathway,indicate damage to the visual network.Bidirectional transsynaptic degeneration may be a potential pathogenic mechanism underlying visual pathway damage in RRMS patients.更多还原