肖俊豪 權巍 許強 吳志軍 楊昉 孫康健 盧光明 張志強
2.排除標準 (1)左利手。(2)常規MRI檢查存在除海馬硬化外的其他顱內病灶。(3)合并其他神經系統疾病及其他嚴重系統性疾病。
3.一般資料 選擇2009年7月-2016年10月在解放軍南京總醫院明確診斷為單側內側顳葉癲的患者共計40例,根據發作類型分為部分性發作和繼發全面性發作。(1)部分性發作組(mTLE?PS組):共20例,男性5例,女性15例;年齡18~40歲,平均(27.60±8.43)歲;病程1個月至31年,中位病程12.00(1.58,21.00)年;左側發作 10例,右側 10例。(2)繼發性全面性發作組(mTLE?sGS組):共20例,男性6例,女性14例;年齡18~45歲,平均(28.17±9.26)歲;病程3個月至37年,中位病程10.83(1.42,19.25)年;左側發作 10例,右側 10例。(3)正常對照組:選擇同期在我院進行體格檢查的健康志愿者共20例,男性5例,女性15例;年齡19~42歲,平均(27.55±7.77)歲。3組受試者性別(χ2=0.170,P=0.918)和年齡(F=0.250,P=0.975)比較,差異無統計學意義;兩組內側顳葉癲患者病程比較,差異亦無統計學意義(Z=0.298,P=0.766),均衡可比。
1.頭部MRI檢查 受試者以醫用海綿墊固定頭部、耳塞降低噪音,采用德國Siemens公司生產的Magnetom Trio Tim 3.0T MRI掃描儀,8通道頭部線圈,梯度場強40 mT/m,進行矢狀位T1?三維磁化準備快速梯度回波(T1?3D?MPRAGE)掃描,掃描參數為:重復時間(TR)2300 ms、回波時間(TE)298 ms、反轉時間(TI)400 ms,翻轉角(FA)9°,掃描視野(FOV)256 mm×256 mm,矩陣256×256,激勵次數(NEX)為1次,層厚 1 mm、層間距為零,掃描時間590 s,共176層,掃描范圍覆蓋全腦。同時行T1WI、T2WI、擴散加權成像(DWI)和 T2?FLAIR 成像。(1)T1WI:重復時間280 ms、回波時間2.50 ms,掃描視野240 mm×240 mm,矩陣256×320,激勵次數2次,層厚5 mm、層間距6.50 mm,掃描時間92 s,共掃描30層,掃描范圍覆蓋全腦。(2)T2WI:重復時間 4000 ms、回波時間98 ms,掃描視野240 mm×240 mm,矩陣307×512,激勵次數2次,層厚5 mm、層間距6.50 mm,掃描時間 90 s,共 30層,掃描范圍覆蓋全腦。(3)DWI序列:重復時間3000 ms、回波時間91 ms,掃描視野218 mm×240 mm,矩陣174×192,激勵次數2次,層厚為5 mm、層間距6.50 mm,掃描時間59 s,共掃描36層,掃描范圍覆蓋全腦。(4)T2?FLAIR 成像:重復時間8000 ms、回波時間93 ms,掃描視野199 mm×220 mm,矩陣232×256,激勵次數2次,層厚5 mm、層間距6.50 mm,掃描時間114 s,共掃描28層,掃描范圍覆蓋全腦。
2.圖像處理與數據分析 采用MRIcron軟件包(http://www.mricro.com)將DICOM格式文件轉換為Nifti_1格式圖像;將左側海馬硬化患者的圖像進行鏡面翻轉,統一將右側海馬硬化定義為患側、左側定義為健側;采用VBM8軟件(http://dbm.neuro.uni-jena.de/vbm8)分割成灰質、白質和腦脊液,通過VBM法獲得相對體積和全腦體積;將獲得的灰質圖像進行8 mm×8 mm×8 mm半高全寬(FWHM)的高斯平滑處理。針對灰質體積,采用SPM8軟件(http://www.fil.ion.ucl.ac.uk/spm)建立廣義線性模型,采用單因素方差分析,剔除性別、年齡、全腦體積等協變量的影響,族錯誤率(FWE)校正后以P≤0.01為差異具有統計學意義,獲得統計腦圖。選取內側顳葉癲患者雙側額葉和丘腦作為興趣區(ROI),以全腦體積作為協變量,分析各腦區灰質體積與病程的相關性。
3.統計分析方法 采用SPSS 23.0統計軟件進行數據處理與分析。計數資料以相對數構成比(%)或率(%),采用χ2檢驗。正態性檢驗采用Kolomogorov?Simirnov檢驗,呈正態分布的計量資料以均數±標準差表示,采用單因素方差分析,兩兩比較行LSD?t檢驗;呈非正態分布的計量資料以中位數和四分位數間距[M(P25,P75)]表示,采用Mann?Whitney U檢驗。內側顳葉癲患者各腦區灰質體積與病程的相關性采用Spearman秩相關分析。以P≤0.05為差異具有統計學意義。
3組受試者雙側額上回、右側額中回、右側額內側回、右側角回、右側顳中回、右側海馬、雙側丘腦和雙側小腦半球灰質體積差異有統計學意義(均P<0.01,FWE校正),與正常對照者相比,內側顳葉癲患者以致灶側為主的雙側大腦半球廣泛性灰質體積減少,其中,mTLE?PS組主要包括雙側額上回、小腦半球和右側顳中回、海馬、丘腦,mTLE?sGS組主要包括雙側額上回、丘腦、小腦半球和右側角回、顳中回、海馬;與mTLE?PS組相比,mTLE?sGS組雙側額上回、丘腦和右側額內側回、直回灰質體積減少(均P<0.01,FWE校正;圖1;表1,2)。
mTLE?PS組患者左側額上回、右側額中回和雙側丘腦灰質體積與病程無關聯性(均P>0.05);mTLE?sGS組患者左側額上回(rs=?0.611,P=0.004)和右側額中回(rs=?0.562,P=0.010)與病程呈負相關,而雙側丘腦與病程無關聯性(P>0.05,表3)。

圖1 3組受試者各腦區灰質體積的比較(P<0.01,FWE校正) 1a 與正常對照組相比,mTLE?PS組雙側額上回、小腦半球和右側顳中回、海馬、丘腦灰質體積減少(藍色區域所示) 1b 與正常對照組相比,mTLE?sGS組雙側額上回、丘腦、小腦半球和右側角回、顳中回、海馬灰質體積減少(藍色區域所示) 1c 與mTLE?PS組相比,mTLE?sGS組雙側額上回、丘腦和右側額內側回、直回灰質體積減少(藍色區域所示)Figure 1 Comparison of gray matter volumes of brain regions among 3 groups(P<0.01,FWE correction).Compared with control group,gray matter volumes in bilateral superior frontal gyri,bilateral cerebellar hemispheres,right middle temproral gyrus,right hippocampus and right thalamus in mTLE?PS group were significantly decreased(blue areas indicate,Panel 1a).Compared with control group,gray matter volumes in bilateral superior frontal gyri,bilateral thalami,bilateral cerebellar hemispheres,right angular gyrus,right middle temproral gyrus and right hippocampus in mTLE?sGS group were significantly decreased(blue areas indicate,Panel 1b).Compared with mTLE?PS group,gray matter volumes in bilateral superior frontal gyri,bilateral thalami,right medial frontal gyrus and right gyrus rectus in mTLE?sGS group were significantly decreased(blue areas indicate,Panel 1c).

表1 3組受試者灰質體積減少的腦區Table 1. Brain regions with decreased gray matter volumes in 3 groups

表2 3組受試者各腦區灰質體積的兩兩比較Table 2. Paired comparison of gray matter volumes in brain regions of 3 groups

表3 mTLE?PS組和mTLE?sGS組患者各腦區灰質體積與病程的相關分析Table 3. Correlation analysis between gray matter volumes and duration in mTLE?PS group and mTLE?sGS group
[1]Bai ZJ,Zhang ZQ,Lu GM.Development of diffusion tensor imaging in mesial temporal lobe epilepsy[J].Zhongguo Yi Xue Ying Xiang Ji Shu,2010,26:178?180.[白卓杰,張志強,盧光明.磁共振彌散張量成像在內側顳葉癲癇中的應用進展[J].中國醫學影像技術,2010,26:178?180.]
[2]Riederer F,Lanzenberger R,Kaya M,Prayer D,Serles W,Baumgartner C.Network atrophy in temporal lobe epilepsy:a voxel?based morphometry study[J].Neurology,2008,71:419 ?425.
[3]Commission on Classification and Terminology of the InternationalLeague AgainstEpilepsy.Proposalforrevised clinical and electroencephalographic classification of epileptic seizures[J].Epilepsia,1981,22:489?501.
[4]Moran NF,Lemieux L,Kitchen ND,Fish DR,Shorvon SD.Extrahippocampal temporal lobe atrophy in temporal lobe epilepsy and mesial temporal sclerosis[J].Brain,2001,124:167?175.
[5]Zhang ZQ,Liao W,Xu Q,Wei W,Zhou HJ,Yang F,Mantini D,Ji X,Lu G.Hippocampus?associated causal network of structural covariance measuring structural damage progression in temporal lobe epilepsy[J].Hum Brain Mapp,2017,38:753?766.
[6]LabateA,CerasaA,AgugliaU,MumoliL,QuattroneA,Gambardella A.Voxel?based morphometry of sporadic epileptic patients with mesiotemporal sclerosis[J].Epilepsia,2010,51:506?510.
[7]Bernasconi N,Duchesne S,Janke A,Lerch J,Collins DL,Bernasconi A.Whole?brain voxel?based statistical analysis of gray matter and white matter in temporal lobe epilepsy[J].Neuroimage,2004,23:717?723.
[8]Chan CH,Briellmann RS,Pell GS,Scheffer IE,Abbott DF,Jackson GD.Thalamic atrophy in childhood absence epilepsy[J].Epilepsia,2006,47:399?405.
[9]Ciumas C,Savic I.Structural changes in patients with primary generalized tonic and clonic seizures[J].Neurology,2006,67:683?686.
[10]Bertram EH,Scott C.The pathological substrate of limbic epilepsy:neuronal loss in the medial dorsal thalamic nucleus as the consistent change[J].Epilepsia,2000,41:S3?8.
[11]Bertram EH,Mangan PS,Zhang DX,Scott CA,Williamson JM.The midline thalamus:alterations and a potential role in limbic epilepsy[J].Epilepsia,2001,42:967?978.
[12]Meeren HK,Pijn JP,Van Luijtelaar EL,Coenen AM,Lopes da Silva FH.Corticalfocus drives widespread corticothalamic networks during spontaneous absence seizures in rats[J].J Neurosci,2002,22:1480?1495.
[13]Chang BS,Lowenstein DH.Epilepsy[J].N Engl J Med,2003,349:1257?1266.