【作者】 胡崇宇；

【导师】 肖波；

【作者基本信息】 中南大学 ， 神经病学， 2010， 博士

【摘要】 目的：分析部分性发作癫痫患者的认知功能和情绪状态特点；结合血氧水平依赖的功能磁共振成像(BOLD-fMRI)、弥散张量成像(DTI)和三维结构磁共振成像(3D)的多模态磁共振成像,探讨部分性发作癫痫患者与健康对照组静息状态下的脑功能,脑白质的完整性,脑灰质密度和体积的差异。方法：对60例部分性发作癫痫患者和60例性别、年龄和教育程度匹配的正常健康对照者组,采用韦氏数字广度测验、言语流畅性测验及逻辑记忆测验量表进行认知功能评估,采用抑郁自评量表(SDS)和焦虑自评量表(SAS)进行情绪状态评估,分析癫痫患者的认知功能和情绪特点。使用3.0T磁共振采集癫痫患者组和正常对照组的多模态MRI数据包括静息状态下BOLD-fMRI、DTI以及3D。采用局部一致性(ReHo)方法和功能连接方法分析静息状态下的BOLD-fMRI数据；采用基于体素的全脑配准分析(VBA)方法分析DTI的各向异性分数(FA)和表观弥散系数(ADC)；采用基于体素的形态学测量(VBM)方法对3D的脑灰质密度和体积的数据进行分析。结果：共60例部分性发作癫痫患者和60例性别、年龄和教育程度匹配的正常健康者完成磁共振扫描,排除头动导致的数据质量问题,进入统计分析的BOLD-fMRI部分的癫痫患者52例(26男／26女),正常对照组54例(33男／21女)；DTI部分各组例数为56例(26男／30女),60例(38男／22女)；3D部分各组例数为60例(28男／32女),60例(38男／22女)。结果发现：1.癫痫患者组的数字广度、言语流畅性测验的正确数、逻辑记忆测验的即刻记忆和延迟记忆得分均较正常组低,差异具有统计学意义(p=0.000,p=0.000,p=0.000,p=0.000)；言语流畅性测验的重复数和错误数两组之间比较无统计学差异(p=0.107,p=0.227)。复杂部分性发作组和继发全面性发作组间数字广度、言语流畅性测验的正确数和逻辑记忆测验的得分无统计学差异(p=0.439, p=0.473, p=0.403, p=0.228);癫痫患者组SDS评分和SAS评分均较正常组高,具有统计学差异(p=0.001,p=0.001)；复杂部分性发作组和继发全面性发作组间SDS评分和SAS评分无统计学差异(p=0.443, p=0.173)。2.BOLD-fMRI:(1)癫痫患者的左侧顶下小叶、中央后回和中央前回,右侧丘脑、小脑、楔前叶和旁中央小叶,双侧岛叶的ReHo较正常对照组降低,差异具有显著性；未发现局部一致性升高的脑区。(2)癫痫患者组的默认模式网络(DMN)的功能连接主要包括左侧楔前叶／后扣带回和角回、扣带回；正常对照组的功能连接主要包括左侧楔前叶／后扣带回和右侧角回,双侧内侧额叶和颞叶。(3)癫痫患者组的左侧顶下小叶、缘上回、钩回、海马旁回和颞上回,右侧钩回的DMN功能连接较正常对照组降低,差异具有显著性；未发现功能连接升高的脑区。3.DTI：(1)癫痫患者组的左侧海马旁回、钩回、小脑后叶蚓垂、梭状回,右侧颞中回、额中回、尾状核、胼胝体下回、小脑前叶山顶、扣带回、颞叶深部白质、额叶深部白质,双侧颞上回的脑白质FA值较正常对照组低,差异有显著性；癫痫患者组左侧胼胝体、额中回、前扣带回、内侧苍白球的脑白质FA值显著高于正常对照组,差异有显著性。(2)癫痫患者组左侧额中回、额下回、颞上回、颞中回、颞下回和小脑后叶山坡,右侧额叶内侧回、额叶深部、胼胝体下回、海马旁回和小脑后部,双侧梭状回和钩回的脑白质ADC值较正常对照组高,差异有显著性；癫痫患者组无较正常对照组ADC值低的脑区。4.3D：(1)癫痫患者组的双侧豆状核的外侧苍白球和壳核的脑区灰质密度较较正常对照组升高,差异有显著性；癫痫患者组无较正常对照组灰质密度降低的脑区。(2)癫痫患者组左侧额叶眶回、额内侧回、旁中央小叶、颞横回和颞上回,右侧顶下小叶、后扣带回、枕下回和楔叶,双侧中央前回、岛叶、前扣带回、楔前叶和小脑前叶的脑灰质体积较正常对照组降低,差异有显著性；未发现灰质体积升高的脑区。结论：1.部分性发作癫痫患者存在记忆、注意力和语言方面的认知功能损害,并且存在明显的抑郁和焦虑情绪。神经精神量表是客观的评价癫痫患者神经心理状况的方便、有效手段。2.部分性发作癫痫患者静息状态下顶下小叶和顶叶内侧面、额叶中央前回、岛叶、丘脑、边缘叶及颞上回等的脑区的功能及功能连接异常,可能是潜在的病理生理机制。3.部分性发作癫痫患者的广泛的白质完整性和灰质异常,提示神经网络的连接障碍和节点损害,可能是部分性发作癫痫的病理基础,并推测与认知功能和情绪障碍有关。4.常规MRI阴性的部分性发作癫痫患者,通过多模态的磁共振检查,能够发现广泛的脑功能和脑结构改变。更多还原

【Abstract】 Object To analysis the cognitive function and emotional state of the patients with partial epilepsy, and to explore the difference between partial epilepsy subjects and healthy subjects in term of brain function in resting state, white matter integrity, and density and volume of gray matter by using the multi modal MRI including blood oxygenation level dependent functional magnetic resonance imaging(BOLD-fMRI), three dimension MRI(3D) and diffusion tensor imaging(DTI) techniques.Methods 60 patients with partial epilepsy and 60 healthy controls with equivalent gender, age and education level are assessed by digital span test and verbal fluency test of Wechsler adult intelligence scale (WAIS), logic memory test of Wechsler adult memory scale (WMS), self-rating depression scale (SDS), self-rating anxiety scale (SAS).The patients with epilepsy and the health controls undergo multi modal MRI scan including resting-state BOLD-fMRI, DTI and 3D. The regional homogeneity (ReHo) approach and functional connectivity analysis are used to analyze resting-state BOLD-fMRI; the voxel-base analysis (VBA) are used to analyze fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of DTI; while the voxel-based morphometry (VBM) method are used to process the gray matter density and volume data obtained by 3D.Results 60 patients with partial epilepsy and 60 healthy controls with equivalent gender, age and education level recieve MRI scan. Some data are excluded because of head movement. The final data include those from 52 patients (26 males/26 females) and 54 healthy controls (33 males/21 females) in BOLD-fMRI part; 56 patients (26 males/30 females) and 60 healthy controls (38 males/22 females) in DTI part; 60 patients (28 males/32 females) and 60 healthy controls (38 males/22 females) in 3D part. The study finds that:1) Digital span test, immediate and delay logical memory test scores are significantly lower in patients compared with controls(p=0.000, p=0.000, p=0.000). In verbal fluency test, the patients produce significantly less correct words than the controls (p=0.000), and the repeated and error words produced by the patients and the controls are of no significant difference (p=0.107, p=0.227). Digital span test, verbal fluency test and logical memory test scores are similar between the patients with complex partial seizure and secondary generalized seizure (p=0.439, p=0.473, p=0.403, p=0.228). The scores of SDS and SAS are significantly higher in patients compared with controls(p=0.001, p=0.001); The scores of SDS and SAS are of no significant difference between the patients with complex partial seizure and secondary generalized seizure(p=0.443, p=0.173).2) As far as BOLD-fMRI data are concerned:(1) ReHo analysis:patients with partial epilepsy showed significantly decreased ReHo in left inferior parietal lobule, postcentral gyrus and precentral gyrus, right thalamus, cerebellum, precuneus and paracentral lobule, bilateral insula compared with control subjects; no region with significantly increased ReHo in patients is found. (2) Default mode network (DMN):The DMN of patients include left precuneus and adjacent posterior cingulate cortex (Pcu/PCC), angular gyrus, cingulate gyrus; the DMN of controls include left Pcu/PCC, right angular gyrus, bilateral medial frontal lobe and temporal lobe. (3) Functional connectivity:Compared with control subjects, patient with partial epilepsy show significantly decreased functional connectivity of DMN region in left inferior parietal lobule, supramarginal gyrus, parahippocampa gyrus and superior temporal gyrus, bilateral uncus; while no region with significantly increased functional connectivity in patients is found.3) As far as DTI data are concerned:(1) Compared with healthy controls, patients with partial epilepsy show significantly decreased FA values in left parahippocampa gyrus, uncus, cerebellum posterior lobe uvula, fusiform gyrus, right middle temporal gyrus, middle frontal gyrus, caudate, subcallosal gyrus, cerebellum anterior lobe culmen, cingulate gyrus, temporal lobe and frontal lobe sub-gyral white matter, bilateral superior temporal gyrus; while significantly increased FA values in left corpus callosum, middle temporal gyrus, anterior cingulate and medial globus pallidus. (2) Compared with healthy controls, patients with partial epilepsy show significantly increased ADC values in left middle frontal gyrus, inferior frontal gyrus, superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus and cerebellum posterior lobe declive, right medial frontal gyrus, frontal lobe sub-gyral white matter, Subcallosal Gyrus, subcallosal gyrus, parahippocampa gyrus and posterior cerebellum, bilateral fusiform gyrus and uncus; while no region with significantly decreased ADC value in patients is found.4) As far sa 3D data are concerned:(1) Compared with healthy controls, patients with partial epilepsy show significantly increased gray matter density in bilateral lateral globus pallidus and Putamen; while no region with significantly decreased gray matter density in patients is found. (2) Compared with healthy controls, patients with partial epilepsy show significantly decreased gray matter volume in left orbital gyrus, medial frontal gyrus, paracentral lobule, transverse temporal gyrus and superior temporal gyrus, right inferior parietal lobule, posterior cingulate, inferior occipital gyrus and cuneus, bilateral precentral gyrus, insula, anterior cingulate, precuneus and anterior cerebellum lobe; while no region with significantly increased gray matter volume in patients is foundConclusions 1. The cognitive function of the partial epilepsy patients is impaired, with depression and anxiety as common symptoms in the patients. The neuropsychic scale is the convenient and effective method to estimate the neuropsychic state of epilepsy patients.2. The resting-state brain function and functional connectivity is abnormal in in left inferior parietal lobule, medial parietal lobe, precentral gyrus, insula, thalamus, limbic lobe and superior temporal gyrus of partial epilepsy patients. It may be the potential pathophysiological mechanism.3. The wide abnormality in integrity of white matter and gray matter suggest a extensive neural network disorder that might be the neuropathological basis of partial epilepsy and correlate with the impaired cognition, depression and anxiety.4. The multi modal MRI can detect the extensive changes of brain function and structure in MRI-negative partial epilepsy.更多还原