特發(fā)全面性癲基底節(jié)丘腦皮質(zhì)環(huán)路的多模態(tài)MRI研究進展

呂貴文　范國光*

呂貴文范國光*

特發(fā)性全面性癲日是一組非局灶性發(fā)病且沒有明確病因的癲日綜合征。其發(fā)病原因至今不明，之前有研究推測丘腦皮質(zhì)環(huán)路起著重要作用，目前通過MRI新技術(shù)的研究，發(fā)現(xiàn)了基底節(jié)-丘腦-皮質(zhì)環(huán)路可能影響癲日發(fā)作的產(chǎn)生和傳播。常規(guī)MRI未能發(fā)現(xiàn)異常改變，而擴散張量成像、基于體素的形態(tài)測量學分析及靜息態(tài)功能MRI的多模態(tài)MR新技術(shù)可從結(jié)構(gòu)、體積及功能三方面發(fā)現(xiàn)該環(huán)路的異常改變，就其最新研究進展予以綜述。

特發(fā)性全面性癲日；擴散張量成像；基于體素的形態(tài)測量學；靜息態(tài)功能磁共振成像

Int J Med Radiol，2016，39（5）:505-508

1　基底節(jié)-丘腦-皮質(zhì)環(huán)路

前輻射冠、上輻射冠與內(nèi)囊前肢、內(nèi)囊后肢分別組成了丘腦前輻射以及丘腦上輻射，這些丘腦輻射連接丘腦與大腦皮質(zhì)（主要是額葉皮質(zhì)），丘腦輻射與大腦白質(zhì)纖維束之間的連接稱為丘腦-皮質(zhì)環(huán)路[7-8]。Alexander等[9]提出從基底節(jié)經(jīng)過丘腦將信息投射到額葉的特定區(qū)域，從而組成5條平行的又相互獨立的閉合的基底節(jié)-丘腦-皮質(zhì)環(huán)路。

丘腦是皮質(zhì)和皮質(zhì)下投射系統(tǒng)的主要中繼站，丘腦的神經(jīng)傳入來源包括初級感覺、基底節(jié)、小腦和大腦的邊緣系統(tǒng)，這些不同的傳入神經(jīng)到達整合和處理信息的特定的丘腦中繼核團，然后將信息傳遞到大腦皮質(zhì)[10]。所以，丘腦是皮質(zhì)和皮質(zhì)下結(jié)構(gòu)、邊緣和皮質(zhì)之間的信息傳遞的關(guān)鍵所在，丘腦核團能夠調(diào)節(jié)癲發(fā)作的易感性并且影響癲發(fā)作的傳播。

基底節(jié)傳入有2個主要輸入核團：紋狀體和底丘腦，它們接收從大腦皮質(zhì)、邊緣結(jié)構(gòu)及丘腦的直接傳入，然后通過直接或間接通路到達主要輸出核——內(nèi)側(cè)蒼白球和黑質(zhì)網(wǎng)狀部，輸出核直接投射到丘腦、中腦和延髓，間接經(jīng)過丘腦投射到達特定皮質(zhì)及邊緣系統(tǒng)[11-12]。Rektor等[13]研究基底節(jié)-丘腦-額葉皮質(zhì)環(huán)路的認知功能（如注意力、運動準備及感覺處理等方面），發(fā)現(xiàn)基底節(jié)可能在認知信息處理方面起到綜合性作用。最近da Silva Braga等[14]記錄到GSW波放電額葉占70%，基底節(jié)占12%，表明這兩個區(qū)域之間的連接為癲樣活動的起始或傳播起到至關(guān)重要的作用。

2　基底節(jié)-丘腦-皮質(zhì)環(huán)路纖維束研究

擴散張量成像（diffusion tensor imaging,DTI）是一種無創(chuàng)性檢測水分子擴散的大小和方向的神經(jīng)成像技術(shù)，通過定量分析各向異性分數(shù)（fractional anisotropy,FA）及平均擴散率（mean diffusivity,MD）來探究纖維束的完整性。擴散峰度成像（diffusion kurtosis imaging,DKI）是DTI技術(shù)的延伸，可以檢測水分子非高斯方向運動，更好地反映組織的微結(jié)構(gòu)改變[15]。

Deppe等[4]首次報道了JME病人內(nèi)囊前肢的FA值減低，隨后，O’Muircheartaigh等[16]發(fā)現(xiàn)JME病人胼胝體（膝部及體部）的完整性被破壞。Focke等[17]報道了IGE病人胼胝體、皮質(zhì)脊髓束、上下縱束以及輔助運動區(qū)（supplementary motor area,SMA）廣泛FA減低；Lee等[18]通過DKI技術(shù)發(fā)現(xiàn)了IGE病人更廣泛的白質(zhì)纖維束的破壞，包括上下輻射冠、內(nèi)囊前后肢、胼胝體（全部）、上縱束以及丘腦輻射。丘腦前輻射是丘腦和內(nèi)囊前肢與前額葉皮質(zhì)之間神經(jīng)纖維束，其完整性的破壞，反映丘腦與雙側(cè)額葉間解剖連接的障礙，而胼胝體膝和體部主要連接雙側(cè)前額葉、前運動區(qū)以及SMA[7]。這些纖維束的破壞可以推測丘腦-皮質(zhì)環(huán)路的障礙。然而，最近有研究[19]報道通過胼胝體切開術(shù)發(fā)現(xiàn)僅能減輕IGE的癥狀，但不能完全改善其癥狀，推測可能正是由于存在皮質(zhì)下其他環(huán)路所致。

一些研究發(fā)現(xiàn)基底節(jié)參與丘腦-皮質(zhì)環(huán)路，Keller等[20]報道了JME病人額葉白質(zhì)纖維束以及殼核的FA值減低，Luo等[21]發(fā)現(xiàn)CAE病人雙側(cè)丘腦、殼核及左側(cè)尾狀核的MD值增加，雙側(cè)尾狀核的FA值減低。這些研究的不一致性可能是由于IGE的亞型不同所致。由于不同亞型間存在互相重疊的臨床表現(xiàn)以及缺乏特異性EEG表現(xiàn)，故臨床區(qū)分非常困難。目前已有研究[22]利用DTI區(qū)分JME與GTCS白質(zhì)纖維束破壞的差異，這提示DTI技術(shù)可能鑒別IGE的不同亞型。大多數(shù)研究沒有發(fā)現(xiàn)DTI參數(shù)值與癲持續(xù)時間、藥物治療間的相關(guān)性，僅Kim等[23]發(fā)現(xiàn)發(fā)作頻率與FA、MD呈正相關(guān)，這提示FA、MD可能作為潛在的生物學指標反映IGE的病理進程?；坠?jié)的研究目前相對較少，有待于以后更多大樣本的研究。

3　基底節(jié)-丘腦-皮質(zhì)環(huán)路體積的研究

基于體素的形態(tài)測量學（voxel based morphometry, VBM）是一種完全自動化的、公正、全面的比較腦組織結(jié)構(gòu)區(qū)域差異的技術(shù)，是一種以體素為單位的形態(tài)測量學方法，可分析腦灰質(zhì)體積成分的差異[24]。

大部分研究發(fā)現(xiàn)各個亞型IGE病人丘腦體積的減小，Kim等[25]報道的JME病人以及Huang等[26]報道的GTCS病人，其丘腦體積均有不同程度的萎縮。但丘腦的亞區(qū)域不同，Wang等[27]發(fā)現(xiàn)背內(nèi)側(cè)核及丘腦枕的體積減少，右側(cè)前內(nèi)側(cè)丘腦[28]以及雙側(cè)前內(nèi)側(cè)丘腦[29]也有報道。然而也有研究[30-31]未發(fā)現(xiàn)JME病人以及混合-IGE病人丘腦體積的改變。雖然有研究[32]報道顳葉上中下回體積的減小，但皮質(zhì)體積減小主要集中在額葉。Tae等[33]發(fā)現(xiàn)前額葉皮質(zhì)灰質(zhì)濃度下降，Kim等[25]發(fā)現(xiàn)內(nèi)側(cè)額葉皮質(zhì)灰質(zhì)體積下降，還有研究[27-28]發(fā)現(xiàn)額葉眶回以及額中央?yún)^(qū)域的萎縮。這些發(fā)現(xiàn)的不一致性可能由于VBM取決于局部灰質(zhì)的平均分割，沒有考慮到皮質(zhì)的折疊，另外IGE的亞型不同也可能造成差異。

一些研究發(fā)現(xiàn)了基底節(jié)區(qū)灰質(zhì)體積的減小。Ciumas等[34]發(fā)現(xiàn)丘腦、腦干、尾狀核以及殼核體積的減小。Du等[5]發(fā)現(xiàn)左側(cè)丘腦、左側(cè)殼核、雙側(cè)蒼白球體積減小，最近Luo等[21]發(fā)現(xiàn)雙側(cè)丘腦、殼核以及蒼白球體積減小。這些研究結(jié)果均支持基底節(jié)-丘腦-皮質(zhì)環(huán)路參與癲發(fā)作的調(diào)控。

4　基底節(jié)-丘腦-皮質(zhì)環(huán)路功能的異常

靜息態(tài)功能MRI(resting-state functional MRI，rs-fMRI)是在靜息狀態(tài)下，通過測量大腦自發(fā)低頻（0.01～0.08 Hz）的血氧水平依賴（blood oxygenation level dependent,BOLD）波動的時間相干性來反映大腦自發(fā)神經(jīng)活動。EEG-fMRI結(jié)合了EEG高時間分辨率和fMRI高空間分辨率的優(yōu)點，在研究腦癲上有很大優(yōu)勢。

在IGE病人的EEG-fMRI研究中，BOLD信號改變與癲放電活動有關(guān)，BOLD信號增高反映癲的易化區(qū)，主要集中在丘腦、尾狀核以及丘腦[35-37]；BOLD信號減低結(jié)果較一致，主要集中在默認網(wǎng)絡(luò)（default mode network，DMN）區(qū)域[38-39]。Wang等[40]用低頻振幅（amplitude of low-frequency fluctuation，ALFF）技術(shù)發(fā)現(xiàn)前額葉皮質(zhì)在0.010～0.027 Hz頻帶有差異，而丘腦則在0.027～0.073 Hz頻帶有差異，這兩個區(qū)域共同在0.198～0.250 Hz波段有差異。除了大腦自發(fā)活動功能的異常外，腦的功能和結(jié)構(gòu)也是密不可分的，Wang等[27]利用功能連接（functional connectivity，F(xiàn)C）技術(shù)，將種子點選在IGE病人丘腦背內(nèi)側(cè)核，發(fā)現(xiàn)雙側(cè)眶額葉皮質(zhì)、尾狀核、殼核和杏仁核中功能連接顯著下降。Kim等[28]最近亦使用FC技術(shù)，發(fā)現(xiàn)IGE病人丘腦前內(nèi)側(cè)與雙側(cè)內(nèi)側(cè)前額葉和楔前葉/后扣帶回功能連接下降。Luo等[6]提出基底節(jié)網(wǎng)絡(luò)概念，并且發(fā)現(xiàn)IGE病人在非放電期間，雙側(cè)尾狀核、殼核功能連接增強，而在放電期間功能連接更強，且增強的連接性與放電的數(shù)目正相關(guān)，因此推測基底節(jié)網(wǎng)絡(luò)在IGE疾病中可能作為一個癲的調(diào)節(jié)器角色。

5　基底節(jié)-丘腦-皮質(zhì)環(huán)路與認知障礙的關(guān)系

這些神經(jīng)認知研究結(jié)果與基底節(jié)-丘腦-額葉皮質(zhì)環(huán)路的功能成像結(jié)果相一致[23]。由于DTI等技術(shù)發(fā)現(xiàn)腦白質(zhì)纖維束損傷的證據(jù)越來越多，使得臨床認知區(qū)域白質(zhì)受損得到越來越多的認可。但是，尚未有研究發(fā)現(xiàn)認知功能評分與DTI參數(shù)之間的相關(guān)性，這可能需要當認知水平下降更嚴重時，以及縱向研究來發(fā)現(xiàn)認知變化與DTI之間的因果關(guān)系，從而有利于病人的治療及預后。

6　局限性與前景

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（收稿2015-08-20）

Study progress of multimodal MRI in basalganglia-thalamocortical circuit of idiopathic generalized epilepsy

LüGuiwen,FAN Guoguang.Department of Radiology,First Affiliated Hospital of China Medical University,Shenyang 110001,China

Idiopathic generalized epilepsy is a group of epileptic disorders without structural brain abnormalities and clear pathogeny of epilepsy syndrome.The etiology is still unknown.Previous studies have speculated that thalamocortical circuit plays an important role.Currently through the research of new MR technologies,the basalganglia-thalamocortical circuit is considered to be responsible for the generation and propagation of seizures.Conventional MRI can’t detect abnormalities,but multimodal new MRI technologies of diffusion tensor imaging,voxel based morphometry and resting-state functional MRI can find abnormal changes in this circuit from structure,volume and function.In this paper,we reviewed the recent progress of those MRI technologies.

Idiopathic generalized epilepsy;Diffusion tensor imaging;Voxel based morphometry;Resting-state functional MRI

10.19300/j.2016.Z3698

R741.02；R445.2

A

中國醫(yī)科大學附屬第一醫(yī)院放射科，沈陽110001

范國光，E-mail：cjr.fanguoguang@vip.163.com

*審校者