經(jīng)顱磁刺激技術(shù)在兒童康復(fù)領(lǐng)域的應(yīng)用課件

1、經(jīng)顱磁刺激技術(shù)在兒童康復(fù)的應(yīng)用一、經(jīng)顱磁刺激技術(shù)概述何謂經(jīng)顱磁刺激？ transcranial magnetic stimulation （TMS） Baker 于1985年首先創(chuàng)立的一種電生理技術(shù)利用磁線圈的時(shí)變電流產(chǎn)生時(shí)變脈沖磁場(chǎng)，作用于大腦皮層產(chǎn)生感應(yīng)電流來改變皮層神經(jīng)細(xì)胞的動(dòng)作電位，從而影響神經(jīng)活動(dòng)和腦內(nèi)代謝的磁刺激技術(shù)具有非侵入性、無痛、穿透力強(qiáng)、安全可靠、操作簡(jiǎn)便等優(yōu)點(diǎn) 腦科學(xué)研究領(lǐng)域四大技術(shù)正電子發(fā)射斷層掃描（PET） 功能核磁共振 （fMRI）腦磁圖（MEG）經(jīng)顱磁刺激（TMS）TMS的基本原理 TMS是在一組高壓大容量的電容上充電，用電子開關(guān)向磁場(chǎng)刺激線圈放電，在0.2毫秒內(nèi)

2、流過數(shù)千安培的脈沖電流，瞬時(shí)功率達(dá)到幾十兆瓦，線圈產(chǎn)生的脈沖磁場(chǎng)峰值可達(dá)14T，強(qiáng)大的瞬變磁場(chǎng)可以毫無損耗地穿過顱骨，根據(jù)電磁感應(yīng)原理，在線圈下的顱內(nèi)大腦皮質(zhì)產(chǎn)生反向感應(yīng)電流，刺激局部大腦神經(jīng)細(xì)胞，引起興奮和抑制，產(chǎn)生一系列生理生化反應(yīng)。TMS的作用機(jī)制可引起多種神經(jīng)遞質(zhì)的釋放（多巴胺、5-羥基氨、谷氨酸等）并調(diào)制受體的敏感性；TMS對(duì)即早基因（immediate early genes）表達(dá)的影響, TMS引起皮質(zhì)較廣泛的c-fos、c-jun基因表達(dá)增加，轉(zhuǎn)錄因子CREB磷酸化、mRNA表達(dá)增加；通過改變腦血流、代謝，及內(nèi)分泌功能而發(fā)揮作用；高頻rTMS，可使神經(jīng)元興奮性增加，低頻刺激則有

3、抑制作用。TMS分類刺激脈沖分類單脈沖經(jīng)顱磁刺激（single-pulse TMS，sTMS）雙脈沖經(jīng)顱磁刺激（paired pulse TMS，pTMS）重復(fù)性經(jīng)顱磁刺激（repetitive transcranial magnetic stimulation，rTMS）刺激頻率分類低頻（5HZ）高頻（5HZ）運(yùn)動(dòng)誘發(fā)電位motor evoked potentials（MEP） MEP是用磁（或電）刺激運(yùn)動(dòng)皮質(zhì)或其傳出通路，在刺激點(diǎn)下方通路及效應(yīng)器所記錄到的電反應(yīng)。MEP可較為客觀地反映運(yùn)動(dòng)皮質(zhì)的興奮性，定量評(píng)估中樞運(yùn)動(dòng)傳導(dǎo)功能。 在皮質(zhì)神經(jīng)元至脊髓前角運(yùn)動(dòng)神經(jīng)元通路上任何部位的損害均可導(dǎo)致

4、MEP的異常，表現(xiàn)為閾值、潛伏期及中樞運(yùn)動(dòng)傳導(dǎo)時(shí)間的改變。 運(yùn)動(dòng)誘發(fā)電位主要指標(biāo)閾值（motor threshold）MEP波幅皮質(zhì)潛伏期（cortical latency，CL）皮質(zhì)靜止期（cortical silent period，CSP）中樞運(yùn)動(dòng)傳導(dǎo)時(shí)間（CMCT）二、兒童期神經(jīng)發(fā)育下腦結(jié)構(gòu)的改變突觸的修剪和精化生后第12年神經(jīng)突觸過度生成；生后第2年直至青春期中期，過多的突觸將被修剪，代之以功能依賴的突觸聯(lián)系的精化。視皮層的突觸修剪精化過程較運(yùn)動(dòng)皮層早。Johnston MV. Injury and plasticity in the developing brain. Exp Ne

5、urol,2003(184):S37S41.腦回化隨神經(jīng)發(fā)育，腦回外形也將發(fā)生改變；腦回化的個(gè)體發(fā)育主要在新生兒期，腦回發(fā)育成熟對(duì)TMS-MEP的影響可在生后6周出現(xiàn)。Armstrong E, Schleicher A, Omran H, Curtis M, Zilles K. The ontogeny of human gyrification. Cereb Cortex 1995;5:5663.白質(zhì)的髓鞘化皮質(zhì)脊髓束的髓鞘化主要在生后第2年完成，而皮層下及胼胝體白質(zhì)的髓鞘化較晚，直至成人期早期尚未完成。腦白質(zhì)髓鞘化的順序：從下向上，從后向前，由中央白質(zhì)向周邊白質(zhì)，最后為皮層下白質(zhì)。線圈直徑

6、頭圍大小Interestingly, despite the smaller head circumferences in children, brain volume in humans remains remarkably similar from 6 years of age onwards with only a small reduction in volume for infants and children under 6 years of age (Bartholomeusz et al., 2002).不同年齡兒童TMS-MEP相關(guān)指數(shù)的特點(diǎn)特殊疾病的研究Cerebral p

7、alsyhemiplegia ADHDRett syndromeEpilepsyFreidreich ataxiaPelizaeus-Merzbacher diseaseadrenoleukodystrophy三、TMS技術(shù)在兒童神經(jīng)康復(fù)領(lǐng)域的研究發(fā)育中兒童運(yùn)動(dòng)誘發(fā)電位指標(biāo)的特點(diǎn)閾值10歲兒童MEP閾值較成人高，到青春期降至成人水平；(Garvey et al., 2003；Moll et al., 1999；Nezu et al., 1997)兒童與成人一致，靜息閾值較易化后的運(yùn)動(dòng)閾值高；(Garvey et al., 2003)6歲的兒童，靜息下即使以最大刺激強(qiáng)度也可能引不出可靠的MEP；

8、(Koh and Eyre, 1988)而在靶肌肉興奮下，即使是新生兒MEP亦可引出(Eyre et al., 2001)Age-Related Changes in the Motor Evoked Potential (MEP)MEP threshold was obtained using a focal coil both when the target muscle (first dorsal interosseus FDI) was at rest (RMT) and when there was background muscle activation (AMT). Percen

9、tage of maximum stimulator intensity is represented on the Y axis. Age group is represented on the X axis. Group 1 = 6 to 7 year old children(n=5); Group 2 = 8 to 9 year old children(n=8); Group 3 = 10 to 11 year old children (n=10); Group 4 = 12 to 13 year old children (n=8); Group 5 = adults (n=9)

10、. Open boxes represent RMT, hatched boxes represent AMT. Error bars represent 1 standard deviation from the mean. Note that thresholds get lower with age and that, for all age groups, lower stimulation intensities are required to obtain the AMT. From Garvey MA & Gilbert DL, Transcranial Magnetic Sti

11、mulation in Children, Eur J Paediatr Neurol 2004; 8: 719.MEP latency靜息下與易化的CMCT的發(fā)育規(guī)律不同，35歲易化下的CMCT達(dá)到成熟；靜息下的CMCT則到青春期早期亦未成熟。(Eyre et al., 1991；Fietzek et al., 2000；Kohand Eyre, 1988；Mller et al., 1994)學(xué)齡前兒童的“l(fā)atency jump”是成人的4倍；(Abbruzzese and Trompetto, 2002； Rossini et al., 1994).Cortical silent pe

12、riodsCSP的個(gè)體化發(fā)育體現(xiàn)皮質(zhì)抑制性神經(jīng)元和胼胝體體部白質(zhì)髓鞘化的程度；學(xué)齡前兒童CSP缺失，直至67歲才可始見確定的CSP；(Heinen et al.,1998b)67歲階段與成熟相比較，CSP潛伏期延長(zhǎng)而時(shí)程縮短，此后幾年中潛伏期逐漸縮短，而時(shí)程逐漸增加，至青春期早期達(dá)到成熟水平。(Garvey et al., 2003)The figure shows three EMG tracings of the iSP from a 7 year old boy (upper), a 12 year old girl (middle), and a 22 year old man (lo

13、wer).Maturation of the Ipsilateral Silent PeriodJulia Vry,et al. Exp Brain Res,2008(186):611-618.平均年齡11.9 2.1歲，GMFCS level 1:n=3, 2:n=2, 3:n=6,4:n=4,5:n=0English-language studies using rTMS in persons under the age of 18, yielding 6 published reports. Because rTMS is typically delivered at or above

14、1 Hz for psychiatric indications, our search was confined to these frequencies. Also included are studies involving rTMS above 1 Hz for non-psychiatric indications. Articles were retrieved from the MEDLINE database. There were 19 reported subjects under age 18 who have been administered rTMS at a frequency above 1 Hz: 10 for major depression, 5 for spastic cerebral palsy and 4 for epilepsia partialis continua. We found that most subjects responded favorably to rTMS and no adverse events have been reported. However data are insufficient for drawing firm conc