基于三维脑结构MRI定量分析研究迟发型视神经脊髓炎谱系疾病

A pilot study of late-onset neuromyelitis optica spectrum disorder disease based on brain three-dimensional structural MRI

目的基于三维(3D)脑结构MRI定量分析探讨迟发型视神经脊髓炎谱系疾病(LO-NMOSD)患者的脑结构损伤模式及其与临床神经心理量表评分的关系。方法前瞻性纳入2016年1月至2018年12月在吉林大学第一医院接受诊治的缓解期视神经脊髓炎谱系疾病患者(NMOSD组),按首次发病年龄是否大于50岁,分为LO-NMOSD亚组和早发型NMOSD(EO-NMOSD)亚组。另招募年龄、性别与NMOSD患者匹配的健康志愿者为对照组。采集所有受试者头颅3D脑T1WI、T2液体衰减反转恢复序列成像资料并分析所有受检者的临床资料、神经心理学评分等。采用基于体素的形态学及病灶分割工具技术对MRI数据进行定量分析获得总灰质体积(GMV)、脑灰质分数(GMF)、脑白质分数(WMF)、脑白质高信号分数(WMHF)等指标。以协方差分析比较LO-NMOSD亚组与EO-NMOSD亚组、NMOSD组与对照组脑结构的差异。采用偏相关分析GMF、WMHF与患者临床资料、神经心理量表评分及WMHF与GMF、WMF的相关性。结果NMOSD组47例,男7例、女40例,年龄18~66岁,其中LO-NMOSD亚组20例、EO-NMODS亚组27例;对照组50名,男13名、女37名,年龄18~77岁。与对照组比较,LO-NMOSD亚组患者右侧尾状核GMV缩小(t=3.33,P<0.05),EO-NMOSD亚组患者双侧额颞叶多处脑区GMV缩小(FDR校正P<0.05),与NMOSD组基本一致。校正年龄后,LO-NMOSD与EO-NMOSD组间WMHF差异无统计学意义(F=0.22,P=0.644)。LO-NMOSD亚组全脑GMF与扩展残疾状态量表(EDSS)评分呈负相关(r=-0.53,P=0.025),NMOSD组WMHF与年复发率、EDSS评分呈正相关(r值分别为0.35、0.35,P值分别为0.017、0.018),其余指标均无相关性(P>0.05)。EO-NMOSD亚组WMHF与GMF、WMF呈负相关(r值分别为-0.76、-0.70,P<0.001),NMOSD组患者WMHF与GMF、WMF呈负相关(r值分别为-0.38、-0.55,P<0.05),LO-NMOSD亚组者WMHF与GMF、WMF无相关性(P>0.05)。结论LO-NMOSD患者脑灰质萎缩的范围、部位及其与WMHF的相关性与EO-NMOSD不同,提示LO-NMOSD患者可能具有不同的脑结构损伤模式。

Objective To explore the different patterns of brain structural abnormalities in patients with delayed neuromyelitis optica pedigree disease(LO-NMOSD)and its relationship with clinical neuropsychological scale score based on the quantitative analysis of three-dimensional(3D)brain structure MRI.Methods Patients with neuromyelitis optica pedigree disease in remission(NMOSD group)who received treatment at Jilin University First Hospital from January 2016 to December 2018 were prospectively included and divided into LO-NMOSD subgroup and early-onset NMOSD(EO-NMOSD)subgroup according to whether the age of first onset was>50 years.Another age-and sex-matched healthy volunteers with NMOSD patients were recruited as the control group.3D brain T1WI and T2 fluid-attenuated inversion recovery sequence imaging were acquired,and clinical data,neuropsychological scores of all subjects were analyzed.Total gray matter volume(GMV),cerebral gray matter fraction(GMF),cerebral white matter fraction(WMF),and cerebral white matter high signal fraction(WMHF)were obtained by quantitative analysis of MRI data using voxel-based morphology and lesion segmentation tool techniques.Analysis of covariance was used to compare the differences in brain structure between LO-NMOSD subgroup and EO-NMOSD subgroup,NMOSD group and control group.Partial correlation analysis was used to analyze the correlation between GMF,WMHF and patient clinical data,neuropsychological scale scores,and the correlation between WMHF and GMF,WMF.Results There were 47 cases in the NMOSD group,including 7 males and 40 females aged 18-66 years.Among them,there were 20 cases in the LO-NMOSD subgroup and 27 cases in the EO-NMODS subgroup.The control group consisted of 50 individuals(13 males and 37 females,aged 18 to 77 years).Compared with the control group,the GMV of the right caudate nucleus in the LO-NMOSD group was reduced(t=3.33,P<0.05),and the GMV of multiple brain regions in the bilateral frontal and temporal lobes in the EO-NMOSD group was reduced considerably(FDR corrected,P<0.05),which was consistent with the NMOSD group.After adjusting for age,there was no statistically significant difference in WMHF between the LO-NMOSD and EO-NMOSD groups(F=0.22,P=0.644).The LO-NMOSD subgroup showed a negative correlation between global GMF and the extended disability status scale(EDSS)score(r=-0.53,P=0.025).WMHF in the NMOSD group was positively correlated with annual recurrence rate and EDSS(r=0.35 and 0.35,respectively,and P=0.017 and 0.018,respectively),while other indicators were not correlated(P>0.05).The EO-NMOSD subgroup WMHF showed a negative correlation with GMF and WMF(r=-0.76,-0.70,respectively,P<0.001).The NMOSD group showed a negative correlation between WMHF and GMF,WMF(r=-0.38,-0.55,respectively,P<0.05).There was no correlation between WMHF and GMF,WMF in the LO-NMOSD subgroup(P>0.05).Conclusions The extent and location of gray matter atrophy in patients with LO-NMOSD are different from those of EO-NMOSD.The correlation between WMHF and brain structural changes and clinical data is different between the two groups of patients.These suggest that LO-NMOSD patients may have different patterns of brain structural damage.