结构及功能多模态磁共振成像对GTCS癫痫的研究
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摘要
癫痫是一种常见的中枢神经系统疾病,其生理特征为神经元放电的异常兴奋和神经元活动的同步性增高。原发全面强直-阵挛性癫痫(Epilepsy with Generalized Tonic–Clonic Seizures, GTCS)是癫痫中的一种常见类型,主要临床症状为肌肉僵硬、四肢抽搐、意识丧失等,传统的神经影像并不能检查出与其症状相关的器质性病变,严重影响GTCS患者的临床诊断和治疗。因此对GTCS患者结构形态和功能受损区域的检测显得尤为重要。
本文旨在通过结构形态和静息态功能磁共振成像对GTCS患者进行多模态的分析,为揭示GTCS的病理生理机制提供有价值的参考依据。论文主要研究内容及创新点如下:
1.采用基于体素形态学(Voxel- Based Morphometry,VBM)的分析方法对GTCS患者进行结构形态研究,发现GTCS患者双侧丘脑、双侧额叶、双侧岛叶和双侧小脑的灰质体积比正常人要低,揭示了GTCS患者存在的大脑结构性异常,且GTCS患者双侧丘脑和额叶区域的灰质体积和其发病病程呈负相关,说明丘脑皮层网络在全身性癫痫发作中受到了直接的伤害。
2.应用局域一致性(Regional Homogeneity, ReHo)和低频振幅(Amplitude of Low Frequency Fluctuation, ALFF)的分析方法对GTCS患者进行静息态功能磁共振研究,发现GTCS患者的双侧丘脑、小脑、脑干、岛叶等区域的ReHo升高,默认网络区域的ReHo降低;GTCS患者的双侧丘脑、岛叶、小脑、额上回和右侧尾状核区域的ALFF升高。ALFF和ReHo的异常增高揭示了GTCS患者在这些区域的BOLD低频振荡强度异常增高和神经元活动同步性的增高,从功能上反映了这些区域的异常情况。
通过上述研究发现,GTCS患者ReHo、ALFF异常增高的区域和其灰质体积减少的区域非常的相似,说明这些区域不仅存在功能上的异常,同时存在结构上的损伤,且损伤的区域聚集在小脑-丘脑-皮层通路上,可能是神经元长时间处于高度同步活跃的异常情况下,而导致其结构上也出现了损伤。
Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. Epilepsy with generalized tonic–clonic seizures (GTCS) represents a common subsyndrome of Idiopathic generalized epilepsies (IGE), characterized by typical seizure symptoms of muscle rigidity, tic of limbs and loss of consciousness. Visual inspection of structural MRI in GTCS patients is usually normal. So it is significant to detect regional subtle structural abnormalities and resting-state functional abnormalities in the GTCS patients.
The aim of our research is to investigate the abnormal region in the GTCS patients using structural and resting-state functional MRI analysis, which will provide significant clues for the study of pathophysiological mechanism of epilepsy. The main contents and innovations of this thesis are as follows:
1. Using voxel- based morphometry (VBM), we found that GTCS patients showed significantly gray matter (GM) volume reductions in the bilateral thalami, frontal lobe, insula and cerebellum, suggesting that there are structural abnormalities in these regions involved in generalized epilepsies. In addition, the bilateral thalamic and left medial frontal gyrus GM volume had a negative correlation with the duration of epilepsy, which indicates that epilepsy may directly impair the thalamus and frontal lobe.
2. Regional homogeneity (ReHo) and Amplitude of low frequency fluctuation (ALFF) were used to investigate functional abnormalities in the GTCS patients. Compared with the healthy controls, GTCS patients showed increased ReHo in the bilaterally thalami, cerebellum, brain stem and insula regions, decreased ReHo mainly in default mode network (DMN). In addition, increased ALFF regions were observed in the bilaterally thalami, cerebellum, insula, superior frontal gyrus and right caudate nucleus.
These findings demonstrate that the regions of reduced GM volume are similar with the ones of increased ReHo and ALFF in the GTCS patients and mainly distributed in the cerebello-thalamo-cortical pathways, reflecting that these regions not only exist functional abnormalities but also subtle structural abnormalities. The current results suggest that the neurons may have structural impairment when long-term under conditions of high excitability and synchronization.
本文旨在通过结构形态和静息态功能磁共振成像对GTCS患者进行多模态的分析,为揭示GTCS的病理生理机制提供有价值的参考依据。论文主要研究内容及创新点如下:
1.采用基于体素形态学(Voxel- Based Morphometry,VBM)的分析方法对GTCS患者进行结构形态研究,发现GTCS患者双侧丘脑、双侧额叶、双侧岛叶和双侧小脑的灰质体积比正常人要低,揭示了GTCS患者存在的大脑结构性异常,且GTCS患者双侧丘脑和额叶区域的灰质体积和其发病病程呈负相关,说明丘脑皮层网络在全身性癫痫发作中受到了直接的伤害。
2.应用局域一致性(Regional Homogeneity, ReHo)和低频振幅(Amplitude of Low Frequency Fluctuation, ALFF)的分析方法对GTCS患者进行静息态功能磁共振研究,发现GTCS患者的双侧丘脑、小脑、脑干、岛叶等区域的ReHo升高,默认网络区域的ReHo降低;GTCS患者的双侧丘脑、岛叶、小脑、额上回和右侧尾状核区域的ALFF升高。ALFF和ReHo的异常增高揭示了GTCS患者在这些区域的BOLD低频振荡强度异常增高和神经元活动同步性的增高,从功能上反映了这些区域的异常情况。
通过上述研究发现,GTCS患者ReHo、ALFF异常增高的区域和其灰质体积减少的区域非常的相似,说明这些区域不仅存在功能上的异常,同时存在结构上的损伤,且损伤的区域聚集在小脑-丘脑-皮层通路上,可能是神经元长时间处于高度同步活跃的异常情况下,而导致其结构上也出现了损伤。
Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. Epilepsy with generalized tonic–clonic seizures (GTCS) represents a common subsyndrome of Idiopathic generalized epilepsies (IGE), characterized by typical seizure symptoms of muscle rigidity, tic of limbs and loss of consciousness. Visual inspection of structural MRI in GTCS patients is usually normal. So it is significant to detect regional subtle structural abnormalities and resting-state functional abnormalities in the GTCS patients.
The aim of our research is to investigate the abnormal region in the GTCS patients using structural and resting-state functional MRI analysis, which will provide significant clues for the study of pathophysiological mechanism of epilepsy. The main contents and innovations of this thesis are as follows:
1. Using voxel- based morphometry (VBM), we found that GTCS patients showed significantly gray matter (GM) volume reductions in the bilateral thalami, frontal lobe, insula and cerebellum, suggesting that there are structural abnormalities in these regions involved in generalized epilepsies. In addition, the bilateral thalamic and left medial frontal gyrus GM volume had a negative correlation with the duration of epilepsy, which indicates that epilepsy may directly impair the thalamus and frontal lobe.
2. Regional homogeneity (ReHo) and Amplitude of low frequency fluctuation (ALFF) were used to investigate functional abnormalities in the GTCS patients. Compared with the healthy controls, GTCS patients showed increased ReHo in the bilaterally thalami, cerebellum, brain stem and insula regions, decreased ReHo mainly in default mode network (DMN). In addition, increased ALFF regions were observed in the bilaterally thalami, cerebellum, insula, superior frontal gyrus and right caudate nucleus.
These findings demonstrate that the regions of reduced GM volume are similar with the ones of increased ReHo and ALFF in the GTCS patients and mainly distributed in the cerebello-thalamo-cortical pathways, reflecting that these regions not only exist functional abnormalities but also subtle structural abnormalities. The current results suggest that the neurons may have structural impairment when long-term under conditions of high excitability and synchronization.
引文
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[2] Good CD, Johnsrude IS, Ashburner J, et al. A voxel - based morphometric study of ageing in 465 normal adult human brains [J]. Neuroimage, 2001, 14(1pt1): 21~36.
[3] Ogawa S, Tank D, Menon R, et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping using MRI [J]. Proc Natl Acad Sci USA, 1992, 89(13): 5951~5955.
[4] Zhang D, Raichle ME. Disease and the brain's dark energy [J]. Nat Rev Neurol, 2010, 6 (1):15~28.
[5] Fox MD, Greicius M. Clinical applications of resting state functional connectivity [J]. Front Syst Neurosci, 2010, 17: 4~19.
[6] Waites AB, Briellmann RS, Saling MM, et al. Functional connectivity networks are disrupted in left temporal lobe epilepsy [J]. Ann Neurol, 2006, 59 (2): 335~343.
[7] Engel J, Pedley TA, eds. Epilepsy, a comprehensive textbook [M]. Philadelphia: Lippincott Williams & Wilkins, 1997: 133~157, 323~341.
[8] Tae WS, Joo EY, Kim JH, et al. Cerebral perfusion changes in mesial temporal lobe epilepsy: SPM analysis of ictal and interictal SPECT [J]. Neuroimage, 2005, 24 (1): 101~110.
[9] Wright IC, McGuire PK, Poline JB, et al. A voxel based method for the statistical analysis of gray and white matter density applied to schizophrenia [J]. Neuroimage, 1995, 2 (4): 244~252.
[10] Ashburner J, Friston KJ. Voxel-based morphometry-the methods [J]. Neuroimage, 2000, 11 (6 Pt 1): 805~821.
[11]伊慧明,李威.基于体素的形态学测量在阿尔茨海默病研究中的应用[J].国际医学放射学杂志,2009,32(2):116~119.
[12] Bonilha L, Rorden C, Castellano G, et al. Voxel-based morphometry reveals gray matter network atrophy in refractory medial temporal lobe epilepsy [J]. Arch. Neurol, 2004, 61 (9): 1379~1384.
[13] Avanzini G, Binelli S, Franceschetti S, et al. Pathophysiology of myoclonus in Janz syndrome. In: Schmitz, B., Sander, T. (Eds.). Juvenile Myoclonic Epilepsy: The Janz Syndrome [M]. Petersfield: Wrightson Biomedical Publishing, 2000: 57~72.
[14] Gerardo Maria de Araújo Filho, Andrea Parolin Jackowski, et al. Personality traits related to juvenile myoclonic epilepsy: MRI reveals prefrontal abnormalities through a voxel-based morphometry study [J]. Epilepsy & Behavior, 2009,15 (2): 202~207. [ 15] Chan CH, Briellmann RS, Pell GS, et al. Thalamic atrophy in childhood absence epilepsy [J].Epilepsia, 2006, 47 (2): 399~405.
[16] Zifkin B, Andermann E, Andermann F. Mechanisms, genetics, and pathogenesis of juvenile myoclonic epilepsy [J]. Curr Opin Neurol, 2005, 18 (2): 147~153.
[17] Raichle ME, MacLeod AM, Snyder AZ, et al. A default mode of brain function [J]. Proc Natl Acad Sci USA, 2001, 98(2): 676~682.
[18] Zang YF, Jiang TZ, Lu YL, et a1. Regional homogeneity approach to fMRI data analysis [J]. Neuroimage, 2004, 22(1): 394~400.
[19] Wu, T., X. Long, et al. Regional homogeneity changes in patients with Parkinson's disease [J]. Hum Brain Mapp, 2009, 30 (5): 1502~1510.
[20] Tian LX, Jiang TZ, Liang M, et a1. Enhanced resting-state brain activities in ADHD patients: A fMRI study [J]. Brain & Development, 2008, 30(5): 342~348.
[21] Liu HH, Liu ZN, Liang M, et a1. Decreased regional homogeneity in schizophrenia: a resting state functional magnetic resonance imaging study [J]. Neuroreport, 2006, 17(1): 19~22.
[22] Yuan YG, Zhang ZJ, Bai F, et al. Abnormal neural activity in the patients with remitted geriatric depression: A resting-state functional magnetic resonance imaging study [J]. Journal of Affective Disorders, 2008, 111(2): 145~152.
[23] He Y, Wang L, Zang Y, et al. Regional coherence changes in the early stages of Alzheimer’s disease: A combined structural and resting-state functional MRI study [J]. NeuroImage, 2007, 35(2): 488~500.
[24] Liu Y, Wang K, YU CS, et a1. Regional homogeneity, functional connectivity and imaging markers of Alzheimer’s disease: A review of resting-state fMRI studies [J]. Neuropsychologia, 2008, 46(6): 1648~1656.
[25] Bettus, G., F. Wendling, et al. Enhanced EEG functional connectivity in mesial temporal lobe epilepsy [J]. Epilepsy Res, 2008, 81(1): 58~68.
[26]谭启富,李龄,吴承远等.癫痫外科学[M].北京:人民卫生出版社, 2006, 67~72,439~448.
[27]王怡,黎海涛.特发性全身性癫痫的临床与磁共振波谱研究进展[J].现代生物医学进展, 2006, 6(7): 65~72.
[28] Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes [J]. Epilepsia, 1989, 30 (4): 389~399.
[29]杨正汉,冯逢,王霄英等.磁共振成像技术指南[M].北京:人民军医出版社, 2007: 24~40, 303~305.
[30] Raichle ME. Two views of brain function [J]. Trends Cogn Sci, 2010, 14 (4): 180~190.
[31] Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging [J]. Nat Rev Neurosci, 2007, 8 (9): 700~711.
[32] Raichle ME. The brain's dark energy [J]. Sci Am, 2010, 302 (3): 44~49.
[33] Raichle ME. Neuroscience. The brain's dark energy [J]. Science, 2006, 314 (5803): 1249~1250.
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