榮艷紅，趙琨 ，蘇紅軍，齊金龍

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微栓子監(jiān)測(cè)在腦干梗死和椎基底動(dòng)脈狹窄中的作用

榮艷紅，趙琨 ，蘇紅軍，齊金龍

摘要：目的探討腦干梗死患者微栓子信號(hào)(MES)陽性與椎基底動(dòng)脈狹窄的關(guān)系。方法156例急性腦干梗死患者進(jìn)行頭顱核磁共振成像和CT血管造影檢查，確定腦梗死病灶及椎基底動(dòng)脈狹窄情況，并于發(fā)病7 d內(nèi)應(yīng)用經(jīng)顱多普勒經(jīng)枕窗進(jìn)行基底動(dòng)脈MES監(jiān)測(cè)，分為MES陰性組136例及陽性組20例?？疾?組一般資料及不同狹窄程度；椎基底動(dòng)脈狹窄患者中2組不同部位情況；Logistic回歸分析MES陽性表達(dá)的影響因素。結(jié)果2組年齡、性別、高血壓病史及糖尿病史等差異均無統(tǒng)計(jì)學(xué)意義；不同狹窄程度的構(gòu)成差異有統(tǒng)計(jì)學(xué)意義，陰性組以無或輕度狹窄為主，陽性組以重度狹窄最高（P＜0.05）。無椎基底動(dòng)脈狹窄70例，輕、中及重度狹窄86例均為椎基底動(dòng)脈狹窄，其中MES陽性者14例，陰性者72例。椎基底動(dòng)脈狹窄患者的2組在不同狹窄部位差異有統(tǒng)計(jì)學(xué)意義，陰性組各狹窄部位比例差異不大，而陽性組顱內(nèi)椎基底動(dòng)脈狹窄率高于85%（P＜0.05），陽性組多部位梗死比例高于陰性組（P＜0.05）。顱內(nèi)椎基底動(dòng)脈狹窄、椎基底動(dòng)脈狹窄75%以上為MES陽性的獨(dú)立危險(xiǎn)因素。結(jié)論重度狹窄的椎基底動(dòng)脈更易出現(xiàn)后循環(huán)系統(tǒng)的MES，導(dǎo)致腦梗死；微栓子可能是椎基底動(dòng)脈狹窄出現(xiàn)多部位腦梗死的發(fā)病原因。

關(guān)鍵詞：腦干梗死；椎基底動(dòng)脈狹窄；微栓子；經(jīng)顱多普勒超聲

作者單位：天津市寶坻區(qū)人民醫(yī)院神經(jīng)內(nèi)科（郵編301800）

1　資料與方法

1.1一般資料選取2012年1月—2013年10月于本院神經(jīng)內(nèi)科確診為腦干梗死的患者156例，符合1995年全國第4屆腦血管病學(xué)術(shù)會(huì)議制定的腦梗死診斷標(biāo)準(zhǔn)，采用第9屆國際腦血流動(dòng)力學(xué)會(huì)議制定的MES識(shí)別標(biāo)準(zhǔn)：（1）時(shí)間短暫，＜300 s。（2）信號(hào)強(qiáng)度高于背景血流信號(hào)＞3 dB。（3）單方向出現(xiàn)于血流頻譜中。（4）伴有尖銳哨聲或鳥鳴聲，均經(jīng)頭顱磁共振成像（MRI）和頭顱CT血管造影（CTA）檢查確診。除外不能配合MES監(jiān)測(cè)及MRI等檢查者，156例中無溶栓者；男109例，女47例，年齡35～78歲；合并高血壓111例、糖尿53例、腦卒中病史35例、心房纖顫2例、吸煙史66例。

1.2方法（1）MES監(jiān)測(cè)。所有患者發(fā)病7 d內(nèi)，采用德國DWL公司的Doooler BOX TCD檢測(cè)儀，經(jīng)枕窗進(jìn)行基底動(dòng)脈MES監(jiān)測(cè)，監(jiān)測(cè)時(shí)間持續(xù)30 min，設(shè)置MES相對(duì)強(qiáng)度閾值＞3 dB；患者坐位或側(cè)臥位，監(jiān)測(cè)頭架旋轉(zhuǎn)90°，經(jīng)枕窗監(jiān)測(cè)基底動(dòng)脈，雙深度探頭取樣深度80～95 mm，容積8 mm。由經(jīng)過培訓(xùn)的專人負(fù)責(zé)MES監(jiān)測(cè)，每個(gè)MES均經(jīng)回放確認(rèn)，并經(jīng)2名神經(jīng)科醫(yī)生同時(shí)確認(rèn)。根據(jù)有無監(jiān)測(cè)到MES分為MES陽性組和陰性組。156例中MES陽性組20例(12.8%)，陰性組136例（87.2%）。（2）狹窄程度判斷。所有患者進(jìn)行包含磁共振擴(kuò)散加權(quán)成像(DWI)的MRI和CTA檢查，DWI檢查采用帶有標(biāo)準(zhǔn)化頭線圈的1.5 T核磁掃描儀(Gyroscan ASC NT, Philips Medical Systems)。用0、313和1 252 s/mm2不同值獲得3個(gè)基本磁場(chǎng)方向的9個(gè)層面。至少在2個(gè)DWI中出現(xiàn)高強(qiáng)度信號(hào)才能被認(rèn)為是急性腦梗死。CTA應(yīng)用美國GE LightSpeed VCT型CT檢查，根據(jù)管腔狹窄和信號(hào)丟失的程度，將椎基底動(dòng)脈狹窄分成無狹窄、輕度狹窄(＜50%)、中度狹窄（50%～75%）及重度狹窄(＞75%)。

1.3統(tǒng)計(jì)學(xué)方法采用SPSS 13.0統(tǒng)計(jì)軟件包進(jìn)行數(shù)據(jù)處理。符合正態(tài)分布的計(jì)量資料用x ±s表示，2組間均數(shù)比較應(yīng)用t檢驗(yàn)。計(jì)數(shù)資料以例（%）表示，組間比較用χ2檢驗(yàn)。多因素分析采用Logistic回歸分析。檢驗(yàn)水準(zhǔn)α=0.05。

2　結(jié)果

2.1 2組一般資料及不同狹窄程度結(jié)果比較2組性別、年齡、高血壓病史及糖尿病史等差異均無統(tǒng)計(jì)學(xué)意義，見表1。2組不同狹窄程度的構(gòu)成差異有統(tǒng)計(jì)學(xué)意義，陰性組以無或輕度狹窄為主，陽性組重度狹窄者比例最高（P＜0.05），見表2。

Tab. 1 Comparison of the clinical characteristics between two groups表1 2組一般資料比較

Tab. 2 Comparison of different degrees of VBA stenosis between two groups表2 2組不同狹窄程度的情況比較　例（%）

2.2椎基底動(dòng)脈狹窄患者不同部位情況156例中無椎基底動(dòng)脈狹窄70例、輕度35例、中度18例、重度33例；輕、中及重度狹窄86例均為椎基底動(dòng)脈狹窄，其中MES陽性14例，陰性72例。MES陽性組和陰性組在不同狹窄部位差異有統(tǒng)計(jì)學(xué)意義，陰性組各狹窄部位比例差異不大，而陽性組中顱內(nèi)椎基底動(dòng)脈狹窄率高于85%（P＜0.05），見表3。

Tab. 3 Comparison of different VBA stenosis locations between two groups of patients表3椎基底動(dòng)脈狹窄患者不同狹窄部位的比較例（%）

2.3椎基底動(dòng)脈狹窄患者M(jìn)ES表達(dá)陽性組和陰性組的單一梗死和多部位梗死情況比較陽性組多部位梗死比例高于陰性組（P＜0.05），見表4。

Tab. 4 Comparison of different infarct lesions between two groups of patients表4椎基底動(dòng)脈狹窄患者腦梗死部位比較　例（%）

2.3 MES影響因素分析結(jié)果以MES為因變量（有=1，無=0），以年齡（ 65歲=0，＜65歲=1）、性別（女=0，男=1）、監(jiān)測(cè)時(shí)間（ 24 h=0,＞24 h=1）、動(dòng)脈狹窄（部位和程度）、吸煙、糖尿病、高血壓、冠心病、高脂血癥為自變量（均為無=0，有=1），Logistic多因素回歸分析結(jié)果顯示，顱內(nèi)椎基底動(dòng)脈狹窄、椎基底動(dòng)脈狹窄75%以上為MES的危險(xiǎn)因素（均P＜0.05），見表5。

Tab. 5 The multivariate Logistic regression analysis of factors influencing microembolic signals表5微栓子影響因素的多元Logistic回歸分析

3　討論

目前，MES監(jiān)測(cè)主要應(yīng)用于前循環(huán)腦梗死。Kinsella等[3]研究表明，重度狹窄患者較輕、中度狹窄患者微栓子陽性率高，其中12.2%患者再次出現(xiàn)缺血性腦血管病。Markus等[4]對(duì)70%狹窄以上的無癥狀頸動(dòng)脈狹窄患者進(jìn)行MES監(jiān)測(cè)示，MES陽性患者2年內(nèi)發(fā)生缺血性腦血管病風(fēng)險(xiǎn)是陰性患者的2.54倍。后循環(huán)椎基底動(dòng)脈狹窄的MES監(jiān)測(cè)的報(bào)道少見，主要原因?yàn)楹笱h(huán)血管不易固定頭架監(jiān)測(cè)。Hwang等[5]對(duì)140例急性后循環(huán)缺血性腦血管病患者進(jìn)行MES監(jiān)測(cè)顯示，18例（12.9%）患者出現(xiàn)微栓子，認(rèn)為椎基底動(dòng)脈狹窄是微栓子陽性的獨(dú)立相關(guān)因素，重度椎基底動(dòng)脈狹窄者微栓子出現(xiàn)頻率較輕、中度狹窄者更高，頭MRI出現(xiàn)多病灶的患者微栓子陽性率較單一病灶患者更多。本研究Logistic回歸分析示，顱內(nèi)椎基底動(dòng)脈狹窄、尤其椎基底動(dòng)脈重度狹窄為MES陽性的獨(dú)立危險(xiǎn)因素，而顱外段椎動(dòng)脈狹窄不是MES影響因素。Telman等[6]研究亦顯示，椎基底動(dòng)脈狹窄是腦血管發(fā)生缺血事件和復(fù)發(fā)的重要原因，而椎動(dòng)脈顱外段很少有癥狀。有研究推測(cè)原因可能為椎動(dòng)脈顱外段斑塊所受生物學(xué)剪應(yīng)力小，斑塊較穩(wěn)定，不易破裂產(chǎn)生微栓子[7-8]。

Kinsella等[9]研究認(rèn)為，頸動(dòng)脈狹窄程度越重，MES出現(xiàn)頻率越高。與頸動(dòng)脈狹窄類似，本研究結(jié)果顯示，椎基底動(dòng)脈狹窄（狹窄 50%）較無狹窄或狹窄＜50%MES陽性率高，并且椎基底動(dòng)脈重度狹窄較中度狹窄MES陽性率高，提示椎基底動(dòng)脈狹窄程度嚴(yán)重，MES出現(xiàn)頻率升高。Logistic多因素回歸分析表明椎基底動(dòng)脈狹窄是急性腦梗死MES陽性的主要影響因素，與Hwang等[5]研究結(jié)果一致。有研究認(rèn)為，高度狹窄的血管之所以易于產(chǎn)生MES，可能與血流動(dòng)力學(xué)改變有關(guān)，管腔狹窄越明顯，血流速度越快，沖刷狹窄的血管壁和斑塊所受生物學(xué)剪應(yīng)力就越大，可引起斑塊脫落，同時(shí)當(dāng)血液流經(jīng)狹窄處進(jìn)入較寬的血管腔時(shí)，易于在旋渦處聚集成凝塊，從而產(chǎn)生微栓子，另外也可能與狹窄處的病變組織性質(zhì)和類型不同有關(guān)[10]。

本研究86例有椎基底動(dòng)脈狹窄，MES陽性組較陰性組腦梗死病灶增多，表明椎基底動(dòng)脈狹窄患者的微栓子可能是多部位腦梗死的病因，可能機(jī)制為血管源性微栓子脫落，阻塞了不同小動(dòng)脈，出現(xiàn)缺血，從而表現(xiàn)為急性腦梗死的各種臨床癥狀。雖然一些研究提到后循環(huán)狹窄患者有DWI的嚴(yán)重病變，但該文未探討椎基底動(dòng)脈狹窄的腦梗死發(fā)生機(jī)制[11]。一般情況下，DWI顯示的多部位梗死是腦梗死栓塞發(fā)生機(jī)制的標(biāo)志，而應(yīng)用MES監(jiān)測(cè)和DWI病變分析有助于發(fā)現(xiàn)腦梗死患者的發(fā)病機(jī)制。

綜上所述，對(duì)于椎基底動(dòng)脈狹窄的患者可以通過枕窗進(jìn)行基底動(dòng)脈MES監(jiān)測(cè)，重度狹窄的椎基底動(dòng)脈更易出現(xiàn)后循環(huán)系統(tǒng)的MES，導(dǎo)致腦梗死；微栓子可能是椎基底動(dòng)脈狹窄出現(xiàn)多部位腦梗死的發(fā)病原因。

參考文獻(xiàn)

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（2015-07-27收稿2015-10-23修回）

（本文編輯陸榮展）

應(yīng)用研究

The role of microembolic signal monitoring in brainstem infarction and vertebrobasilar artery stenosis

RONG Yanhong, ZHAO Kun , SU Hongjun, QI Jinlong
Neurology Department, Baodi People′s Hospital, Tianjin 301800, China Corresponding Author E-mail:rongrong790125@163.com

Abstract:Objective To investigate the relation between microembolic signals (MES) and vertebral basilar artery ste?nosis in patients with brainstem infarction. Methods A total of 156 patients with acute brainstem infarction, who were de?termined the cerebral infarction lesion and vertebral basilar artery stenosis by cranial magnetic resonance imagingand CT an?giography, and were monitored by transcranial Doppler via occipital window of basilar arterial MES monitoring in 7 days of the onset, were divided into microembolus signal negative group (n=136) and positive group (n=20). The clinical data were compared between two groups. The differences of different degrees of stenosis were analyzed in two groups. The differences of different locations of stenosis in patients with vertebral basilar artery stenosis were analyzed in two groups. Logistic regres?sion analysis was used to analyse the factors affecting MES. Results There were no significant differences in age, gender, history of hypertension and diabetes mellitus between the two groups (P＜0.05). There were significant differences in the dif?ferent degrees of stenosis between two groups, no or mild stenosis was found in MES-negative group and severe stenosis in MES-positive group (P＜0.05). There were 70 cases with no vertebral basilar artery stenosis, 86 cases with mild, moderate and severe stenosis, in which 14 cases were MES-positive and 72 cases were negative. There were significant differences in different locations of stenosis between the two groups. The proportion of multiple infarctions was significantly higher in MES-positive group than that of MES-negative group (P＜0.05). The intracranial vertebral basilar artery stenosis and 75% of ver?tebral basilar artery stenosis were the independent risk factors of MES-positive. Conclusion Severe stenosis of the verte?bral basilar artery is more vulnerable to occur MES of posterior circulation, leading to cerebral infarction. Microemboli may be the cause of multiple infarctions in patients with vertebral basilar artery stenosis.

Key words:brain stem infarction; vertebral basilar artery stenosis; microembolic signal; transcranial doppler ultraso?nography目前，微栓子信號(hào)（microembolic signals，MES）監(jiān)測(cè)已經(jīng)廣泛應(yīng)用于缺血性腦卒中。MES在預(yù)測(cè)頸內(nèi)動(dòng)脈和大腦中動(dòng)脈缺血性卒中方面起著重要的作用，MES監(jiān)測(cè)是判斷顱內(nèi)動(dòng)脈栓子來源的重要依據(jù)[1-2]。但是，目前有關(guān)椎基底動(dòng)脈系統(tǒng)的后循環(huán)和腦干梗死的MES監(jiān)測(cè)研究尚少見相關(guān)報(bào)道。本研究擬通過經(jīng)顱多普勒超聲（TCD）對(duì)腦干梗死患者經(jīng)枕窗行基底動(dòng)脈MES監(jiān)測(cè)，探討腦干梗死患者微栓子與椎基底動(dòng)脈狹窄的關(guān)系。

中圖分類號(hào)：R743.33

文獻(xiàn)標(biāo)志碼：A

DOI：10.11958/20150054

作者簡介：榮艷紅（1979），女，碩士，主要從事腦血管病的研究

通訊作者E-mail：rongrong790125@163.com