楊鳴姝 王 莉 翟 倩 帕米爾 周 劍 曹 云 喬中偉

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·論著·

磁共振形態(tài)學(xué)半定量評(píng)分對(duì)新生兒細(xì)菌性腦膜炎出院結(jié)局的評(píng)估價(jià)值

楊鳴姝1王 莉1翟 倩2帕米爾1周 劍1曹 云2喬中偉1

目的 分析MRI形態(tài)學(xué)半定量評(píng)分對(duì)新生兒細(xì)菌性腦膜炎出院結(jié)局的評(píng)估價(jià)值。方法 收集復(fù)旦大學(xué)附屬兒科醫(yī)院2011年7月至2013年12月NICU收治的出院診斷為新生兒細(xì)菌性腦膜炎的病例，采用基于大腦損傷MRI形態(tài)學(xué)分析的半定量評(píng)分，對(duì)頭顱MRI圖像進(jìn)行回顧性分析。MRI形態(tài)學(xué)評(píng)價(jià)包括腦室擴(kuò)大、腦室旁白質(zhì)容積丟失、腦白質(zhì)囊性病灶、內(nèi)囊后肢髓鞘化異常、皮質(zhì)信號(hào)異常、顱內(nèi)腦外間隙異常、基底節(jié)信號(hào)異常、腦白質(zhì)非囊性信號(hào)異常、腦室內(nèi)出血、腦室積膿、腦膜異常強(qiáng)化、室管膜異常強(qiáng)化和腦膿腫。將上述13項(xiàng)評(píng)分歸納為腦白質(zhì)異常(WMA)、腦灰質(zhì)異常(GMA)和非腦實(shí)質(zhì)異常(NPA)。同時(shí)采集患兒出生孕周、發(fā)病時(shí)間、MRI檢查時(shí)間、發(fā)病至MRI檢查間隔時(shí)間和出院結(jié)局。按照出生孕周分為早產(chǎn)兒組和足月兒組，再按照出院結(jié)局分為預(yù)后良好和預(yù)后不良亞組，在各組內(nèi)比較亞組之間時(shí)間因素、MRI單項(xiàng)評(píng)分和綜合評(píng)分的差異。結(jié)果 63例新生兒細(xì)菌性腦膜炎病例進(jìn)入分析(早產(chǎn)兒組18例，足月兒組45例)。MRI單項(xiàng)評(píng)分構(gòu)成預(yù)后良好和預(yù)后不良亞組間差異有統(tǒng)計(jì)學(xué)意義的指標(biāo)：早產(chǎn)兒組中有腦室擴(kuò)大(P=0.012)和腦室旁白質(zhì)容積丟失(P=0.004)；足月兒組有腦室擴(kuò)大(P=0.002)、腦室旁容積丟失(P=0.040)、顱內(nèi)腦外間隙異常(P=0.005)和腦室內(nèi)出血(P=0.038)。MRI綜合評(píng)分中，早產(chǎn)兒組WMA評(píng)分(P=0.001)和NPA評(píng)分(P=0.039)、足月兒組NPA評(píng)分(P=0.018)在預(yù)后不良和預(yù)后良好亞組之間分布差異有統(tǒng)計(jì)學(xué)意義。足月兒組和早產(chǎn)兒組內(nèi)不同預(yù)后亞組的各時(shí)間因素差異未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)意義或臨床意義。結(jié)論 新生兒細(xì)菌性腦膜炎MRI腦室擴(kuò)大和腦室旁白質(zhì)容積丟失預(yù)示早產(chǎn)兒出院不良結(jié)局；腦室擴(kuò)大、腦室旁白質(zhì)容積丟失、顱內(nèi)腦外間隙異常和腦室內(nèi)出血預(yù)示足月兒出院不良結(jié)局。WMA評(píng)分高預(yù)示早產(chǎn)兒出院不良結(jié)局，NPA評(píng)分高預(yù)示早產(chǎn)兒和足月兒出院不良結(jié)局。

新生兒； 細(xì)菌性腦膜炎； 磁共振成像； 腦損傷； 出院結(jié)局

新生兒細(xì)菌性腦膜炎腦損傷形式多樣，與不良預(yù)后密切相關(guān)[9～12]。常規(guī)MRI和彌散加權(quán)成像可以敏感地發(fā)現(xiàn)腦膜炎時(shí)不同部位的腦損傷[12～14]，可為新生兒細(xì)菌性腦膜炎的診斷、治療及預(yù)后判定提供客觀依據(jù)。但目前尚無(wú)基于MRI的新生兒細(xì)菌性腦膜炎腦損傷的統(tǒng)一分類標(biāo)準(zhǔn)，對(duì)各種MRI影像學(xué)異常與預(yù)后的關(guān)系尚無(wú)系統(tǒng)地闡述；且上述文獻(xiàn)中報(bào)道MRI檢查時(shí)的病程長(zhǎng)短不一，未對(duì)可能與MRI檢查結(jié)果有關(guān)的時(shí)間因素進(jìn)行具體分析。有文獻(xiàn)報(bào)道新生兒顱腦MRI較晚檢查的陽(yáng)性發(fā)現(xiàn)才與預(yù)后相關(guān)[15,16]，早期MRI檢查對(duì)預(yù)后判斷的價(jià)值值得商榷。

筆者在臨床中發(fā)現(xiàn)新生兒細(xì)菌性腦膜炎MRI表現(xiàn)以大腦異常為主，故本文采用基于大腦損傷MRI形態(tài)學(xué)表現(xiàn)的半定量評(píng)分系統(tǒng)，對(duì)復(fù)旦大學(xué)附屬兒科醫(yī)院(我院)NICU收治的新生兒細(xì)菌性腦膜炎病例的頭顱MRI圖像進(jìn)行回顧性分析。初步探討與出院時(shí)預(yù)后有關(guān)的MRI形態(tài)學(xué)表現(xiàn)，同時(shí)分析出生孕周、發(fā)病時(shí)間、MRI檢查時(shí)間是否可能影響MRI結(jié)果的判斷。

1 方法

1.1 納入標(biāo)準(zhǔn) 回顧性收集我院2011年7月1日至2013年12月31日NICU住院患兒出院診斷中含“新生兒腦膜炎”或“化膿性腦膜炎”的病歷。我院新生兒細(xì)菌性腦膜炎的診療常規(guī)主要參考第4版《實(shí)用新生兒學(xué)》[8]，診斷標(biāo)準(zhǔn)主要依據(jù)臨床表現(xiàn)，腦脊液常規(guī)、生化和培養(yǎng)結(jié)果。

1.2 剔除標(biāo)準(zhǔn) ①出院診斷中含以下的病例：先天性畸形或綜合征、先天性TORCH感染、病毒性腦膜炎、神經(jīng)梅毒、結(jié)核性腦膜炎、真菌性腦膜炎、新生兒窒息、新生兒缺氧缺血性腦病和代謝性腦??；②不是因?yàn)槟X膜炎死亡的病例；③出生史不詳?shù)牟±?如棄嬰)；④過(guò)期產(chǎn)兒；⑤病歷記載發(fā)病時(shí)足月兒日齡>28 d，早產(chǎn)兒糾正胎齡>40周；⑥在發(fā)病后未在我院行頭顱MRI檢查者。

1.3 分組考慮 根據(jù)患兒出生孕周分為早產(chǎn)兒組和足月兒組。根據(jù)出院時(shí)的預(yù)后結(jié)局行亞組分析，包括預(yù)后良好亞組和預(yù)后不良亞組。滿足以下一項(xiàng)及以上者定義為預(yù)后不良[17～19]：①出院時(shí)存在神經(jīng)系統(tǒng)癥狀或體征(抽搐、肌張力異常、顱神經(jīng)癱瘓)；②視覺(jué)、聽(tīng)覺(jué)神經(jīng)電生理檢查異常；③全身運(yùn)動(dòng)(GMs)評(píng)估異常；④腦軟化；⑤腦內(nèi)膿腫；⑥需手術(shù)治療的腦積水。不含上述任何一種情況者定義為預(yù)后良好。

1.4 觀察及截取指標(biāo) 本文以新生兒細(xì)菌性腦膜炎出院時(shí)為結(jié)局，分析MRI形態(tài)學(xué)評(píng)分的價(jià)值，與MRI檢查結(jié)果可能有關(guān)的時(shí)間因素。故截取以下資料用于本文分析：①與新生兒細(xì)菌性腦膜炎有關(guān)的臨床表現(xiàn)，腦脊液常規(guī)、生化和培養(yǎng)結(jié)果；②MRI評(píng)分；③MRI評(píng)分與時(shí)間因素(早產(chǎn)兒以糾正胎齡計(jì)，足月兒以生后周齡計(jì))的關(guān)系，新生兒出生孕周，發(fā)病時(shí)間(需要說(shuō)明，發(fā)病時(shí)間以病史明確記錄為準(zhǔn)，如果從病史中不能明確提取發(fā)病時(shí)間，以距腰椎穿刺陽(yáng)性結(jié)果最近的相關(guān)癥狀出現(xiàn)時(shí)間為發(fā)病時(shí)間)，MRI檢查時(shí)間， 發(fā)病至MRI檢查間隔時(shí)間。行多次MRI檢查者，選取首次MRI檢查結(jié)果進(jìn)入本文分析。

1.5 MRI檢查 ①M(fèi)RI設(shè)備為德國(guó)西門(mén)子Avanto 1.5T；②MRI常規(guī)序列包括軸位TSE T2加權(quán)成像、軸位SE/FLASH T1加權(quán)成像、矢狀位SE T1加權(quán)成像、軸位tirm dark-fluid T2加權(quán)成像；軸位DWI采用單次激發(fā)EPI技術(shù)，b值為0和1000 s·mm-2；增強(qiáng)MRI為外周靜脈注射釓雙胺(濃度0.5 mmol·mL-1，劑量0.2 mL·kg-1)后進(jìn)行SE/FLASH T1加權(quán)序列掃描。③MRI檢查前30 min予10%水合氯醛0.5 mL·kg-1口服鎮(zhèn)靜。

1.6 MRI評(píng)分原則

1.7 質(zhì)量控制 收集進(jìn)入分析病例的MRI圖像，由1名放射科主治醫(yī)生在不知曉患兒出院結(jié)局的情況下集中獨(dú)立閱片及評(píng)分，由1名放射科副主任醫(yī)師復(fù)核。

2 結(jié)果

2.1 一般情況 63例進(jìn)入本文分析，病例具體納入和排除流程見(jiàn)圖1。男43例(68.2%)，女20例，出生孕周27.4～41.0(37.8±3.1)周。早產(chǎn)兒18例，男14例，女4例；出生孕周27.4～36.9(33.6±2.7)周。足月兒45例，男29例，女16例；出生孕周37.3～41.0(39.5±0.9)周。32例(50.8%)腦脊液培養(yǎng)或血培養(yǎng)細(xì)菌學(xué)陽(yáng)性；其中19例(30.2%)為腦脊液培養(yǎng)細(xì)菌學(xué)陽(yáng)性(早產(chǎn)兒9例，足月兒10例)，22例(34.9%)為血培養(yǎng)細(xì)菌學(xué)陽(yáng)性(早產(chǎn)兒9例，足月兒13例)，7例(11.1%)為腦脊液培養(yǎng)與血培養(yǎng)細(xì)菌學(xué)均陽(yáng)性且病原菌一致(早產(chǎn)兒2例，足月兒5例)，2例(3.2%)腦脊液培養(yǎng)與血培養(yǎng)細(xì)菌學(xué)均陽(yáng)性但病原菌不一致(早產(chǎn)兒和足月兒各1例)。

1 病例納入和排除流程圖

Fig 1 Flow chart of inclusion and exclusion of patients

2.2 出院結(jié)局情況 表1顯示，早產(chǎn)兒組出院時(shí)預(yù)后良好7例，預(yù)后不良11例；足月兒組出院時(shí)預(yù)后良好24例，預(yù)后不良21例。

表1 63例新生兒細(xì)菌性腦膜炎出院時(shí)結(jié)局[n(%)]

Tab 1 Outcomes at discharge of 63 cases with neonatal bacterial meningitis[n(%)]

OutcomesatdischargePretermgroup(n=18)Termgroup(n=45)NormalCNS7(38.9)24(53.3)AbnormalitiesinCNS11(61.1)21(46.6) Hydrocephalusneedingashunt6(33.3)7(15.6) Hearingimpairment6(33.3)6(13.3) Visionimpairment3(16.7)7(15.6) AbnormalfindinginGMs2(11.1)5(11.1) Intracerebralabscess1(5.6)1(2.2) Encephalomalacia01(2.2) Cranialnerveparalysis01(2.2) Hypertonia02(4.4) Hypotonia01(2.2)

Notes GMs: general movements; CNS: central nervous system

2.3 與MRI檢查結(jié)果可能有關(guān)的時(shí)間因素 表2顯示，足月兒組預(yù)后良好和預(yù)后不良亞組間出生孕周差異有統(tǒng)計(jì)學(xué)意義(P=0.010)；發(fā)病時(shí)間、MRI檢查時(shí)間、發(fā)病至MRI

GAatborn/weeksOnsettimeofmeningitis/weeksAgeatMRIscan/weeksIntervalofonsetandMRIscan/weeksPretermTotal33.6±2.735.5±2.739.2±3.13.6±2.4Cured34.3±1.735.9±2.238.9±2.62.9±1.0Adverse33.2±3.235.2±3.139.3±3.54.1±3.0t0.9430.509-0.297-0.973P0.3600.6180.7700.345TermTotal39.5±0.92.0±2.15.7±3.31.8±1.3Cured39.8±0.62.2±1.13.9±1.41.7±1.4Adverse39.1±0.91.8±1.13.7±1.31.9±1.2t2.7041.2720.520-0.551P0.0100.2100.6060.584

Notes GA: gestational age. The ages of oneset time of meningitis and MRI scan were presented as corrected geatational ages in preterm group while in term group they were presented as chronological ages

檢查間隔時(shí)間在早產(chǎn)兒組和足月兒組中的預(yù)后良好亞組、預(yù)后不良亞組之間差異均無(wú)統(tǒng)計(jì)學(xué)意義(P均>0.05)。

2.4 單項(xiàng)評(píng)分結(jié)果

2.4.1 早產(chǎn)兒組 表3顯示，MRI單項(xiàng)評(píng)分中分值最高的4項(xiàng)為腦室擴(kuò)大(33分)、內(nèi)囊后肢髓鞘化異常(29分)、腦室旁白質(zhì)容積丟失(26分)和腦白質(zhì)囊性病變(26分)。預(yù)后良好和預(yù)后不良亞組間腦室擴(kuò)大、腦室旁白質(zhì)容積丟失分值構(gòu)成差異有統(tǒng)計(jì)學(xué)意義(P分別為0.012和0.004)。余各單項(xiàng)分值構(gòu)成在兩亞組間差異無(wú)統(tǒng)計(jì)學(xué)意義。

2.4.2 足月兒組 表3顯示，MRI單項(xiàng)評(píng)分中分值最高的3項(xiàng)為腦室擴(kuò)大(66分)、顱內(nèi)腦外間隙異常(63分)、腦室積膿(56分)。預(yù)后良好和預(yù)后不良亞組間腦室擴(kuò)大、腦室旁白質(zhì)容積丟失、顱內(nèi)腦外間隙異常和腦室內(nèi)出血分值構(gòu)成差異有統(tǒng)計(jì)學(xué)意義(P分別為0.002, 0.040, 0.005和0.038)。余各單項(xiàng)分值構(gòu)成兩亞組間差異無(wú)統(tǒng)計(jì)學(xué)意義。

2.5 綜合評(píng)分結(jié)果 表4顯示，早產(chǎn)兒組預(yù)后良好和預(yù)后不良亞組相比，WMA和NPA評(píng)分差異有統(tǒng)計(jì)學(xué)意義(P分別為0.001和0.039)。 預(yù)后不良亞組WMA、NPA評(píng)分中位數(shù)均為9分，預(yù)后良好亞組WMA、NPA評(píng)分中位數(shù)均為6分，預(yù)后不良亞組均高于預(yù)后良好亞組；兩亞組GMA評(píng)分差異無(wú)統(tǒng)計(jì)學(xué)意義。足月兒組預(yù)后良好和預(yù)后不良亞組相比，NPA評(píng)分差異有統(tǒng)計(jì)學(xué)意義(P=0.018)，預(yù)后不良亞組NPA評(píng)分中位數(shù)(8分)高于預(yù)后良好亞組(6分)；WMA和GMA評(píng)分差異無(wú)統(tǒng)計(jì)學(xué)意義。

表3 MRI單項(xiàng)評(píng)分與出院時(shí)預(yù)后的關(guān)系

Notes "/": Chi-square test of the brain lesion pattern was Fisher′s exact test without 2 value. "-" represented no case presenting this brain lesion pattern.NA: the item was described as “with” or “without” the character and just had score 1 and score 2 without score 3. Score represented the total score of this brain lesion pattern

表4 早產(chǎn)兒組和足月兒組MRI綜合評(píng)分結(jié)果[M(P25，P75)]

NotesP: The significance of the difference of the distribution about scores between two subgroups; WMA: white matter abormality; GMA: gray matter abormality; NPA: non-brain-parenchyma abormality

3 討論

新生兒、嬰兒期腦膜炎中以細(xì)菌性腦膜炎最常見(jiàn)[5,29]，后遺癥發(fā)生率高[7,8]。目前對(duì)于新生兒細(xì)菌性腦膜炎預(yù)后的研究，無(wú)論是大型回顧性隊(duì)列研究[30～32]還是特殊病原菌的個(gè)例報(bào)道[33, 34]，其中涉及到影像學(xué)表現(xiàn)的報(bào)道有限；而專注于新生兒腦膜炎影像學(xué)表現(xiàn)的研究，則多僅關(guān)注腦白質(zhì)或非腦實(shí)質(zhì)、某一征象或某一MRI技術(shù)在該病診斷和預(yù)后中的價(jià)值[9,14,25]，并未對(duì)腦膜炎腦損傷MRI表現(xiàn)類型進(jìn)行全面評(píng)價(jià)。此外，上述部分研究報(bào)道中對(duì)于腦膜炎病例的選擇標(biāo)準(zhǔn)較寬泛，將細(xì)菌性腦膜炎、病毒性腦膜炎、真菌性腦膜炎或所有新生兒期不同病原的腦膜炎同時(shí)納入研究，并非針對(duì)細(xì)菌性腦膜炎進(jìn)行分析。因此，鑒于新生兒細(xì)菌性腦膜炎的高發(fā)病率和高致殘率，本研究按照新生兒細(xì)菌性腦膜炎的診斷標(biāo)準(zhǔn)[8]，通過(guò)嚴(yán)格的病例篩選，采用涵蓋腦白質(zhì)、腦灰質(zhì)和非腦實(shí)質(zhì)多種腦損傷表現(xiàn)的MRI評(píng)分系統(tǒng)，以期全面分析該疾病大腦損傷MRI表現(xiàn)與預(yù)后的關(guān)系。鑒于本研究為長(zhǎng)期隨訪研究的初步結(jié)果，本文以出院時(shí)結(jié)局作為預(yù)后判斷，對(duì)早產(chǎn)兒和足月兒MRI表現(xiàn)與預(yù)后進(jìn)行相關(guān)分析。

既往研究中發(fā)現(xiàn)MRI檢查結(jié)果可能與患兒出生孕周、發(fā)病時(shí)間、MRI檢查的時(shí)間有關(guān)[16,35]，因此在進(jìn)行MRI表現(xiàn)與預(yù)后關(guān)系分析中，需要首先研究這些時(shí)間因素對(duì)MRI表現(xiàn)結(jié)果的影響。本文結(jié)果顯示足月兒組出生孕周在預(yù)后良好與不良亞組間差異有統(tǒng)計(jì)學(xué)意義，(39.1±0.9)周vs(39.8±0.6)周；兩亞組間差值為0.7周，此差異在臨床實(shí)際工作中并無(wú)臨床意義。其余時(shí)間因素的分析結(jié)果在早產(chǎn)兒和足月兒組中的預(yù)后良好和不良亞組間差異均無(wú)統(tǒng)計(jì)學(xué)意義。表明本研究中患兒出生孕周、發(fā)病時(shí)間、MRI檢查時(shí)間和發(fā)病至MRI檢查間隔時(shí)間對(duì)兩亞組的MRI評(píng)分干擾不大。

本研究結(jié)果提示新生兒細(xì)菌性腦膜炎MRI腦室擴(kuò)大和腦室旁白質(zhì)容積丟失與早產(chǎn)兒出院不良結(jié)局有關(guān)(P<0.05)。而其他單項(xiàng)評(píng)分如顱內(nèi)腦外間隙、腦白質(zhì)非囊性信號(hào)異常、腦室積膿在早產(chǎn)兒預(yù)后良好和預(yù)后不良亞組間差異雖無(wú)統(tǒng)計(jì)學(xué)有意義(P值在0.05～0.1)，但鑒于本研究早產(chǎn)兒樣本量較小，尚無(wú)法明確這些單項(xiàng)評(píng)分與出院結(jié)局的關(guān)系。也有文獻(xiàn)報(bào)道，早產(chǎn)兒中最常見(jiàn)的炎癥相關(guān)性病變是腦白質(zhì)損傷，其特點(diǎn)為局灶性、囊性、腦室周圍白質(zhì)軟化、彌漫性壞死或兼而有之[1]，這些形態(tài)學(xué)的表現(xiàn)與本研究發(fā)現(xiàn)相似。其可能的發(fā)病機(jī)制是早產(chǎn)兒血腦屏障發(fā)育不完善，某些炎性介質(zhì)更容易通過(guò)血腦屏障進(jìn)入腦實(shí)質(zhì)并觸發(fā)“瀑布效應(yīng)”樣連鎖反應(yīng)而導(dǎo)致腦實(shí)質(zhì)損傷；早產(chǎn)兒腦成熟度低(少突膠質(zhì)細(xì)胞前體對(duì)缺血的易感性較強(qiáng))、免疫系統(tǒng)不完善，致使其腦膜炎時(shí)腦白質(zhì)損傷更為明顯[1, 8]。另有研究發(fā)現(xiàn)早產(chǎn)兒斑點(diǎn)狀白質(zhì)病變、腦室擴(kuò)大與長(zhǎng)期預(yù)后中的智力、心理運(yùn)動(dòng)發(fā)育延遲，動(dòng)作發(fā)育延遲以及腦癱顯著相關(guān)[36]。盡管本研究尚未總結(jié)長(zhǎng)期預(yù)后，但出院結(jié)局顯示早產(chǎn)兒腦膜炎若出現(xiàn)MRI腦室擴(kuò)大和腦室旁白質(zhì)容積丟失征象，說(shuō)明出院時(shí)不良預(yù)后是存在的。

足月兒組的結(jié)果顯示腦室擴(kuò)大、腦室旁白質(zhì)容積丟失、顱內(nèi)腦外間隙異常和腦室內(nèi)出血預(yù)示出院結(jié)局不良，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；而腦白質(zhì)非囊性信號(hào)異常分值構(gòu)成在兩亞組間差異非常接近有統(tǒng)計(jì)學(xué)意義(P=0.051)；余MRI單項(xiàng)評(píng)分在兩亞組間差異均無(wú)統(tǒng)計(jì)學(xué)意義。有文獻(xiàn)報(bào)道，足月兒B組鏈球菌腦膜炎可以出現(xiàn)腦室旁白質(zhì)局灶性異常信號(hào)且預(yù)后差[9]；大腸桿菌腦膜炎的足月兒可出現(xiàn)彌漫性白質(zhì)異常信號(hào)伴嚴(yán)重的腦室擴(kuò)大、腦萎縮，后期需要外科手術(shù)治療腦積水[37]。這些研究結(jié)果均說(shuō)明足月兒腦膜炎的腦白質(zhì)損傷、腦室和腦外間隙的腦脊液系統(tǒng)受累所導(dǎo)致的腦損傷與其不良預(yù)后有關(guān)。足月兒腦室和腦外間隙的腦脊液系統(tǒng)受累的特征更接近于嬰兒和兒童腦膜炎[38]，可能與足月兒相對(duì)于早產(chǎn)兒而言其血腦屏障和腦膜血管發(fā)育相對(duì)成熟，作為第一屏障，更易受累有關(guān)。有文獻(xiàn)報(bào)道嬰兒和兒童腦膜炎MRI所見(jiàn)的腦膜彌散加權(quán)異常高信號(hào)預(yù)示不良預(yù)后[39]，與本文觀察到的特征相類似。這也與成人細(xì)菌性腦膜炎研究中發(fā)現(xiàn)的硬膜下積膿與出院時(shí)不良結(jié)局相關(guān)的結(jié)果一致[40]。

大腦白質(zhì)、灰質(zhì)與非腦實(shí)質(zhì)在結(jié)構(gòu)與功能上具有各自的特點(diǎn)，在發(fā)生腦膜炎損傷后可能會(huì)引起不同的神經(jīng)功能障礙。本研究對(duì)MRI的各單項(xiàng)評(píng)分進(jìn)行匯總，歸納為WMA、GMA、NPA三項(xiàng)綜合評(píng)分，旨在分析三者在新生兒細(xì)菌性腦膜炎腦損傷中的發(fā)生情況、嚴(yán)重程度，分析其與出院結(jié)局的關(guān)系。

MRI綜合評(píng)分結(jié)果顯示，WMA評(píng)分高預(yù)示早產(chǎn)兒出院不良結(jié)局。WMA評(píng)分包含腦室擴(kuò)大、腦室旁白質(zhì)容積丟失、內(nèi)囊后肢髓鞘化異常、腦白質(zhì)囊性病變和腦白質(zhì)非囊性信號(hào)異常。如前所述，這些單項(xiàng)均是早產(chǎn)兒腦白質(zhì)損傷的形態(tài)學(xué)表現(xiàn)[1]。與腦室擴(kuò)大和腦室旁白質(zhì)容積丟失單項(xiàng)評(píng)分相比，WMA評(píng)分同樣顯示早產(chǎn)兒腦白質(zhì)損傷與預(yù)后不良相關(guān)，早產(chǎn)兒預(yù)后不良亞組WMA評(píng)分中位數(shù)高于預(yù)后良好亞組。因此采用WMA評(píng)分可以對(duì)預(yù)后判斷進(jìn)行半定量分析。足月兒預(yù)后良好亞組與預(yù)后不良亞組的WMA評(píng)分中位數(shù)均為5分(正常分)，四分位區(qū)間為5～6分，顯示本研究中整個(gè)足月兒組的患兒腦白質(zhì)損傷程度輕，與出院時(shí)預(yù)后無(wú)顯著相關(guān)(P=0.603)。

MRI綜合評(píng)分中的NPA評(píng)分高預(yù)示早產(chǎn)兒和足月兒出院時(shí)不良結(jié)局。NPA包括腦室擴(kuò)大、顱內(nèi)腦外間隙異常、腦室內(nèi)出血、腦室積膿、室管膜和腦膜異常強(qiáng)化。在早產(chǎn)兒組單項(xiàng)評(píng)分中，并未發(fā)現(xiàn)顱內(nèi)腦外間隙信號(hào)異常和腦室積膿在預(yù)后良好和預(yù)后不良亞組間差異有統(tǒng)計(jì)學(xué)意義；而足月兒組單項(xiàng)評(píng)分中，未發(fā)現(xiàn)腦室積膿、室管膜和腦膜異常強(qiáng)化在預(yù)后良好和預(yù)后不良亞組間差異有統(tǒng)計(jì)學(xué)意義。聯(lián)合這些與腦膜和腦脊液系統(tǒng)有關(guān)的損傷類型，提升了亞組之間的差異，預(yù)后不良亞組的NPA評(píng)分均高于預(yù)后良好亞組。

早產(chǎn)兒組和足月兒組的預(yù)后良好亞組與預(yù)后不良亞組的GMA評(píng)分中位數(shù)均為2分，顯示新生兒細(xì)菌性腦膜炎時(shí)腦灰質(zhì)損傷程度輕，與出院預(yù)后無(wú)顯著相關(guān)(P值分別為0.708和0.446)。

MRI形態(tài)學(xué)上腦室擴(kuò)大表現(xiàn)，在新生兒腦膜炎中，既可能是腦實(shí)質(zhì)損傷后的被動(dòng)擴(kuò)大，也可能是腦脊液循環(huán)受阻或腦脊液分泌異常增多所致的腦室擴(kuò)大。雖然在本文病例中沒(méi)有直接證據(jù)來(lái)說(shuō)明腦室擴(kuò)大直接原因，但是文獻(xiàn)報(bào)道腦膜炎患者腦室擴(kuò)大的主要原因是炎癥累及基底池時(shí)，纖維素粘附于蛛網(wǎng)膜上，致使基底池處腦脊液循環(huán)受阻，從而發(fā)生腦積水；同時(shí)由于蛛網(wǎng)膜顆粒的纖維化和粘連致使腦脊液吸收障礙，進(jìn)一步加重腦積水[41]。當(dāng)然也有研究認(rèn)為早產(chǎn)兒腦室擴(kuò)大是由于腦室旁白質(zhì)丟失而導(dǎo)致，因此將其歸為WMA的范疇[15,16,20]。

需要說(shuō)明的是，本研究的設(shè)計(jì)無(wú)法回答腦室內(nèi)出血與腦室擴(kuò)大是否由感染直接導(dǎo)致或?qū)儆诎榘l(fā)征象，本文研究結(jié)果只是反映了腦室內(nèi)出血與足月兒細(xì)菌性腦膜炎出院結(jié)局不良有關(guān)，當(dāng)然本組病例中的腦室內(nèi)出血亦可能是導(dǎo)致腦室擴(kuò)大的因素之一。

本研究不足之處：①以出院時(shí)神經(jīng)系統(tǒng)評(píng)估為結(jié)局指標(biāo)，和臨床最終結(jié)局存在不同，可能會(huì)影響MRI評(píng)分在臨床的應(yīng)用價(jià)值；②樣本量局限，特別是判斷某些單項(xiàng)評(píng)分與預(yù)后的關(guān)系時(shí)統(tǒng)計(jì)效能不高；③由于MRI增強(qiáng)檢查需要增加患兒鎮(zhèn)靜時(shí)間，而MRI平掃已經(jīng)可以提供新生兒科醫(yī)生所關(guān)心的腦損傷改變，所以臨床實(shí)際工作中只有對(duì)懷疑腦膿腫的病例才進(jìn)行頭顱增強(qiáng)MRI檢查；本研究中僅6.3%(4/63)的患兒進(jìn)行了頭顱增強(qiáng)MRI檢查，確診腦膿腫1例，這使得本研究中對(duì)于腦膜、室管膜異常強(qiáng)化征象的觀察受到限制，判斷其與出院結(jié)局的關(guān)系時(shí)會(huì)存在局限。

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(本文編輯：張崇凡)

Predicting the outcomes at discharge of neonatal bacterial meningitis: a semi-quantitative MRI-based-score system analysis

YANGMing-shu1,WANGLi1,ZHAIQian2,PAMi-er1,ZHOUJian1,CAOYun2,QIAOZhong-wei1
(1DepartmentofRadiology; 2DepartmentofNeonatology,Children′sHospitalofFudanUniversity,Shanghai201102,China)

QIAO Zhong-wei，E-mail:qiaozhwei@163.com；CAO Yun，E-mail:yuncaochina@hotmail.com

ObjectiveTo investigate the value of a semi-quantitative MRI-based-score system in predicting outcomes at discharge in infants with neonatal bacterial meningitis.MethodsNewborns with a final diagnosis of neonatal meningitis were included in this study. The severities of thirteen patterns of brain injuries on cranial MR images of the infants were graded, which included ventricular dilatation, periventricular white matter volume loss, cystic abnormality, abnormal myelination of the posterior limb of the internal capsule, cortical gray matter signal abnormality, intracranial extracerebral space abnormality, basal ganglia signal abnormality, non-cystic white matter signal abnormality, intraventricular hemorrhage, pyocephalus, abnormal meningeal enhancement, abnormal ependymal enhancement and encephalopyosis. Except for encephalopyosis, the frequencies of white matter abnormality (WMA), gray matter abnormality (GMA), and non-brain-parenchyma abnormality (NPA) were also calculated. Four time factors and outcomes at discharge were collected from the clinical history of each patient. The patients were divided into preterm and term groups followed by cured and adverse outcome subgroups. The severity and spectrum of different part of cerebral injuries and time factors were compared between two subgroups of each group by using chi-square test, Mann-WhitneyUtest and studentt-test. ResultsSixty-three newborns including 18 preterm infants and 45 term ones were recruited in this study. There were significant differences in the scores of ventricular dilatation and periventricular white matter volume loss between cured and adverse outcome subgroups in preterm group (Pvalue was 0.012 and 0.004, respectively). There were significant differences in the scores of ventricular dilatation, periventricular white matter volume loss, intracranial extracerebral space abnormality, and intraventricular hemorrhage between cured and adverse outcome subgroups in term group (Pvalue was 0.002, 0.040, 0.005 and 0.038, respectively). There were significant differences in the scores of WMA, NPA in preterm group and NPA in term group between two outcome subgroups (Pvalue was 0.001, 0.039 and 0.018, respectively). There was no significant difference with clinical value in time factors between outcome subgroups whether in preterm or term group.ConclusionVentricular dilatation and periventricular white matter volume loss could predict adverse outcomes at discharge in preterm infants with neonatal bacterial meningitis. Ventricular dilatation, periventricular white matter volume loss, intracranial extracerebral space abnormality, and intraventricular hemorrhage could predict adverse outcomes at discharge in term infants with neonatal bacterial meningitis. Regarding to the significance of WMA, GMA and NPA types, high NPA scores could predict adverse outcomes at discharge in both preterm and term infants, while WMA scores could predict adverse outcomes at discharge in preterm ones.

Newborn; Bacterial meningitis; Magnetic resonance imaging； Brain injury； Outcomes at discharge

復(fù)旦大學(xué)附屬兒科醫(yī)院 1 放射科, 2 新生兒科 上海，201102

喬中偉，E-mail:qiaozhwei@163.com；曹云，E-mail:yuncaochina@hotmail.com

10.3969/j.issn.1673-5501.2015.02.005

2015-01-13

2015-03-25)