脊髓小脑共济失调3型的脑灰质结构异常对运动及非运动功能影响的相关研究

Effect of structural abnormality of gray matter on motor and non-motor function in spinocerebellar ataxia type 3

目的 探讨脊髓小脑性共济失调3型(spinocerebellar ataxia type 3,SCA3)患者灰质结构异常及其对非运动性和运动性功能的影响,以期为SCA3的早期诊断、精准治疗提供理论依据。材料与方法102名受试者[49名患者和53名年龄和性别匹配的健康对照(healthy controls,HC)]被纳入研究。参与者接受了神经心理学量表评估,包括蒙特利尔认知评估(Montreal Cognitive Assessment,Mo CA)、简易智力状态检查量表(Mini-mental State Examination,MMSE)、快速词汇测验(Rapid Verbal Retrieval,RVR)、数字跨度测验(Digital Span Test,DST)、日常生活活动能力(Activities of Daily Living,ADL)和汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)以及MRI评估。采用基于体素的形态学分析(voxel-based morphological analysis,VBM)来分析患者与健康对照组之间灰质结构差异。提取差异脑区的灰质体积(gray matter volume,GMV),并与运动及非运动量表进行偏相关分析,以性别、年龄以及颅内总体积(total intracranial volume,TIV)作为协变量。结果与正常对照组相比,SCA3组神经量表评分Mo CA(Z=-4.578,P<0.001)、MMSE(Z=-4.725,P<0.001)和RVR(Z=-5.773,P<0.001)的分数显著下降,ADL(Z=-6.447,P<0.001)和HAMD(Z=-5.285,P<0.001)分数显著升高。SCA3在小脑蚓Ⅸ叶、双侧小脑、尾状核、扣带回、额叶、海马体、中央前回、壳核、辅助运动区和颞叶、左侧距状裂周围皮层、中央旁小叶和海马旁回、右楔叶、梭状回和枕叶存在体积萎缩(P<0.001,FDR校正);体积增加的为丘脑左侧板内核、背内侧核和右腹前核(P<0.001,FDR校正)。差异脑区体积与神经心理学量表偏相关性分析显示:共济失调等级表(Scale for the Assessment and Rating of Ataxia,SARA)和国际合作共济失调评分表(International Cooperative Ataxia Rating Scale,ICARS)评分与蚓部Ⅸ小叶、双侧小脑、中央前回、颞叶、左侧距状裂周围皮层、右侧尾状核、扣带回、额叶、梭状回和枕叶呈负相关,与左侧丘脑板内核呈正相关;Mo CA评分与蚓部Ⅸ小叶和双侧小脑呈正相关;ADL评分与双侧小脑、左侧距状裂周围皮层、颞叶、右梭状回和蚓部Ⅸ小叶呈负相关;HAMD评分与双侧小脑、右额叶、左颞叶呈负相关;RVR评分与双侧小脑、右额叶、左颞叶和蚓部Ⅸ小叶呈正相关。结论SCA3患者的除了小脑结构损伤外,还涉及广泛的认知、记忆、情绪相关脑区损伤,并且与其运动、非运动功能损伤密切相关,这为SCA3下一步的治疗靶区选择提供了理论指导。

Objective:To explore the structural abnormality of gray matter and its effect on non-motor and motor function in patients with spinocerebellar ataxia type 3(SCA3),so as to provide a theoretical basis for early diagnosis and proper treatment of SCA3.Materials and Methods:One hundred and two subjects[49 patients and 53 age-and sex-matched healthy controls(HC)]were enrolled in the study.The participants were assessed by the neuropsychological scale,including the Montreal Cognitive Assessment(MoCA),the Mini Mental State Examination(MMSE),the Rapid Verbal Retrieve(RVR),Digit Span Test(DST),the Activities of Daily Living(ADL),and the Hamilton Depression Scale(HAMD).They also participated in the MRI evaluation.Voxel-based morphometry(VBM)was conducted to analyse the gray matter volume(GMV)alterations between the patients and the healthy controls.The partial correlation analysis was performed to identify the partial correlation between GMV and clinical scale scores with sex,age,and total intracranial volume(TIV)as covariables.Results:Compared with the healthy control group,the scores of MoCA(Z=-4.578,P<0.001),MMSE(Z=-4.725,P<0.001)and RVR(Z=-5.773,P<0.001)in the SCA3 group decreased significantly,while the scores of ADL(Z=-6.447,P<0.001)and HAMD(Z=-5.285,P<0.001)increased significantly.The brain volume atrophied were discovered in the vermisⅨlobe,bilateral cerebellum,caudate nucleus,cingulate gyrus,frontal lobe,hippocampus,precentral gyrus,putamen,supplementary motor area,and temporal lobe,left calcarine cortex,paracentral lobule,and para-hippocampal gyrus,right cuneus,fusiform gyrus and occipital lobe(P<0.001,FDR corrected).The increased ones were intralaminar nucleus,dorsal medial nucleus of left thalamus and ventral anterior nucleus of right thalamus(P<0.001,FDR corrected).The correlation analysis between differential brain area and the neuropsychological scale showed that Scale for the Assessment and Rating of Ataxia(SARA)and International Cooperative Ataxia Rating Scale(ICARS)scores were negatively correlated with the vermisⅨlobule,bilateral cerebellum,precentral gyrus,and temporal lobe;left calcarine cortex,right caudate nucleus,cingulate gyrus,frontal lobe,fusiform gyrus and occipital lobe,while positively correlated with the intralaminar nucleus of left thalamus.MoCA score was positively correlated with vermisⅨlobule and bilateral cerebellum.ADL score was negatively correlated with vermisⅨlobule,bilateral cerebellum,left calcarine cortex,temporal lobe and right fusiform gyrus;HAMD score was negatively correlated with bilateral cerebellum,right frontal lobe and left temporal lobe;RVR score was positively correlated with bilateral cerebellum,right frontal lobe,left temporal lobe andⅨlobule of vermis.Conclusions:In addition to cerebellar structural damage,there are also extensive cognitive,memory and emotional brain damage in SCA3,which is closely related to motor and non-motor functional impairment,which provides theoretical guidance for the next selection of therapeutic targets for SCA3.