抗富含亮氨酸胶质瘤失活蛋白1抗体脑炎患者认知功能与全脑皮层及海马结构改变的相关性

Correlation between cognitive function and structural changes of cerebral cortex and hippocampus in patients with anti-leucine-rich glioma inactivated protein 1 antibody associated encephalitis

目的探讨抗富含亮氨酸胶质瘤失活蛋白1(LGI1)抗体脑炎患者皮层及海马结构改变与认知功能的相关性。方法纳入13例抗LGI1抗体脑炎患者及15名正常对照(对照组),进行神经心理学测试评估其临床症状及认知功能,采集磁共振(MRI)结构像数据,使用基于表面的形态测量分析抗LGI1抗体脑炎患者皮层改变及海马体积,并进一步分析患者大脑结构变化与临床症状及认知功能的相关性,采用支持向量机(SVM)学习分类探索皮层和皮层下海马体积等指标对抗LG1抗体脑炎患者和对照组的鉴别分类情况。结果抗LGI1抗体脑炎患者的蒙特利尔认知评估量表评分(MoCA)(Z=-2.714,P=0.007),中文听觉词汇学习测验(CAVLT)中即刻回忆得分(t=-3.545,P=0.002)、延迟回忆得分(Z=-2.554,P=0.011)、再认回忆正确数(Z=-2.442,P=0.015),言语流畅性测试(VFT)中语义评分(t=-3.062,P=0.005)均显著低于对照组,彩色数字连线测试(CTT)中数字完成时间(Z=-2.742,P=0.006)显著高于对照组。抗LGI1抗体脑炎患者右侧额下回三角部皮层厚度、皮层体积、双侧海马体积显著低于对照组。相关性分析显示,抗LGI1抗体脑炎组右侧额下回三角部皮层厚度与VFT中语义评分呈正相关(r=0.648,P=0.023),左侧海马体积与CAVLT中延迟回忆得分呈显著正相关(r=0.581,P=0.048),右侧海马体积与MoCA评分(r=0.741,P=0.006)以及CAVLT中即刻回忆得分(r=0.755,P=0.005)、延迟回忆得分(r=0.632,P=0.027)呈显著正相关,右侧海马体积与CTT中数字完成时间(r=-0.598,P=0.040)呈显著负相关。右侧额下回三角部皮层厚度、体积及双侧海马体积作为SVM的输入特征,其分类准确率为78.57%,灵敏度为76.92%,特异度为86.67%,受试者工作曲线(ROC)下面积(AUC)为0.8513。结论抗LGI1抗体脑炎患者存在记忆、语言及执行功能等认知功能障碍,且认知功能障碍程度与右侧额下回三角部及双侧海马灰质体积改变相关。抗LGI1抗体脑炎患者特征性脑影像有可能作为早期诊断、病情评估预后检测的指标。

Objective To investigated structural changes of cortex and hippocampus and cognitive function in patients with anti-leucine-rich glioma inactivated protein 1(LGI1)antibody associated encephalitis.Methods Thirteen patients with anti-LGI1 encephalitis and 15 normal controls(NC)were enrolled.Neuropsychological tests were performed to evaluate their clinical symptoms and cognitive function.Magnetic resonance imaging(MRI)data were collected,and surface-based morphometry was used to analyze the cortical changes and hippocampal volume.The correlation between brain structural changes and clinical symptoms and cognitive function was further analyzed.Support vector machine(SVM)learning was used to explore the efficacy of cortical and subcortical hippocampal volume in differentiation between patients with anti-LG1 encephalitis and NC.Results The Montreal cognitive assessment(MoCA)scores(Z=-2.714,P=0.007),immediate recall(t=-3.545,P=0.002),delayed recall(Z=-2.554,P=0.011),and recognition memory correct responses(Z=-2.442,P=0.015)on the Chinese version of the auditory verbal learning test(CAVLT),as well as semantic scores(t=-3.062,P=0.005)on the verbal fluency test(VFT),were all significantly lower in patients with anti-LGI1 encephalitis compared to normal controls(NC).Additionally,completion time on the color trails test(CTT)was significantly higher in patients with anti-LGI1 encephalitis compared to NC(Z=-2.742,P=0.006).In anti-LGI1 encephalitis patients,the cortical thickness,cortical volume and bilateral hippocampal volume of right inferior frontal gyrus triangle were significantly lower than those of NC.Correlation analysis showed that in anti-LGI1 encephalitis group,the cortical thickness of the triangular part of the right inferior frontal gyrus was significantly positively correlated with VFT-semantics(r=0.648,P=0.023),and the volume of the left hippocampus was significantly positively correlated with CAVLT-delayed recall(r=0.581,P=0.048).Right hippocampal volume was positively correlated with MoCA(r=0.741,P=0.006),CAVLT-immediate recall(r=0.755,P=0.005),and CAVLT-delayed recall(r=0.632,P=0.027).Right hippocampal volume was negatively correlated with CTT-number(r=-0.598,P=0.040).The cortical thickness,volume of right inferior frontal gyrus triangularis and bilateral hippocampal volume were used as the input features of SVM.The classification accuracy was 78.57%,the sensitivity was 76.92%,the specificity was 86.67%,and the area under the curve(AUC)was 0.8513.Conclusions Anti-LGI1 encephalitis patients have cognitive impairment such as memory,language,and executive function,which is associated with gray matter volume atrophy in the triangle of right inferior frontal gyrus and bilateral hippocampus.The brain imaging features of anti-LGI1 encephalitis patients can be used as indicators for early diagnosis,disease evaluation,and prognosis prediction.