磁共振形態(tài)學半定量評分對新生兒細菌性腦膜炎出院結(jié)局的評估價值

楊鳴姝 王 莉 翟 倩 帕米爾 周 劍 曹 云 喬中偉

?

·論著·

磁共振形態(tài)學半定量評分對新生兒細菌性腦膜炎出院結(jié)局的評估價值

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)學半定量評分對新生兒細菌性腦膜炎出院結(jié)局的評估價值。方法 收集復旦大學附屬兒科醫(yī)院2011年7月至2013年12月NICU收治的出院診斷為新生兒細菌性腦膜炎的病例，采用基于大腦損傷MRI形態(tài)學分析的半定量評分，對頭顱MRI圖像進行回顧性分析。MRI形態(tài)學評價包括腦室擴大、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)信號異常、顱內(nèi)腦外間隙異常、基底節(jié)信號異常、腦白質(zhì)非囊性信號異常、腦室內(nèi)出血、腦室積膿、腦膜異常強化、室管膜異常強化和腦膿腫。將上述13項評分歸納為腦白質(zhì)異常(WMA)、腦灰質(zhì)異常(GMA)和非腦實質(zhì)異常(NPA)。同時采集患兒出生孕周、發(fā)病時間、MRI檢查時間、發(fā)病至MRI檢查間隔時間和出院結(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)局分為預后良好和預后不良亞組，在各組內(nèi)比較亞組之間時間因素、MRI單項評分和綜合評分的差異。結(jié)果 63例新生兒細菌性腦膜炎病例進入分析(早產(chǎn)兒組18例，足月兒組45例)。MRI單項評分構(gòu)成預后良好和預后不良亞組間差異有統(tǒng)計學意義的指標：早產(chǎn)兒組中有腦室擴大(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綜合評分中，早產(chǎn)兒組WMA評分(P=0.001)和NPA評分(P=0.039)、足月兒組NPA評分(P=0.018)在預后不良和預后良好亞組之間分布差異有統(tǒng)計學意義。足月兒組和早產(chǎn)兒組內(nèi)不同預后亞組的各時間因素差異未發(fā)現(xiàn)統(tǒng)計學意義或臨床意義。結(jié)論 新生兒細菌性腦膜炎MRI腦室擴大和腦室旁白質(zhì)容積丟失預示早產(chǎn)兒出院不良結(jié)局；腦室擴大、腦室旁白質(zhì)容積丟失、顱內(nèi)腦外間隙異常和腦室內(nèi)出血預示足月兒出院不良結(jié)局。WMA評分高預示早產(chǎn)兒出院不良結(jié)局，NPA評分高預示早產(chǎn)兒和足月兒出院不良結(jié)局。

新生兒； 細菌性腦膜炎； 磁共振成像； 腦損傷； 出院結(jié)局

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

筆者在臨床中發(fā)現(xiàn)新生兒細菌性腦膜炎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)學表現(xiàn)的半定量評分系統(tǒng)，對復旦大學附屬兒科醫(yī)院(我院)NICU收治的新生兒細菌性腦膜炎病例的頭顱MRI圖像進行回顧性分析。初步探討與出院時預后有關(guān)的MRI形態(tài)學表現(xiàn)，同時分析出生孕周、發(fā)病時間、MRI檢查時間是否可能影響MRI結(jié)果的判斷。

1 方法

1.1 納入標準 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。我院新生兒細菌性腦膜炎的診療常規(guī)主要參考第4版《實用新生兒學》[8]，診斷標準主要依據(jù)臨床表現(xiàn)，腦脊液常規(guī)、生化和培養(yǎng)結(jié)果。

1.2 剔除標準 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不是因為腦膜炎死亡的病例；③出生史不詳?shù)牟±?如棄嬰)；④過期產(chǎn)兒；⑤病歷記載發(fā)病時足月兒日齡>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)出院時的預后結(jié)局行亞組分析，包括預后良好亞組和預后不良亞組。滿足以下一項及以上者定義為預后不良[17～19]：①出院時存在神經(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、聽覺神經(jīng)電生理檢查異常；③全身運動(GMs)評估異常；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后良好。

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

1.5 MRI檢查 ①MRI設(shè)備為德國西門子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評分原則

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

2 結(jié)果

2.1 一般情況 63例進入本文分析，病例具體納入和排除流程見圖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)細菌學陽性；其中19例(30.2%)為腦脊液培養(yǎng)細菌學陽性(早產(chǎn)兒9例，足月兒10例)，22例(34.9%)為血培養(yǎng)細菌學陽性(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)細菌學均陽性且病原菌一致(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)細菌學均陽性但病原菌不一致(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)兒組出院時預后良好7例，預后不良11例；足月兒組出院時預后良好24例，預后不良21例。

表1 63例新生兒細菌性腦膜炎出院時結(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)的時間因素 表2顯示，足月兒組預后良好和預后不良亞組間出生孕周差異有統(tǒng)計學意義(P=0.010)；發(fā)病時間、MRI檢查時間、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

檢查間隔時間在早產(chǎn)兒組和足月兒組中的預后良好亞組、預后不良亞組之間差異均無統(tǒng)計學意義(P均>0.05)。

2.4 單項評分結(jié)果

2.4.1 早產(chǎn)兒組 表3顯示，MRI單項評分中分值最高的4項為腦室擴大(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)。預后良好和預后不良亞組間腦室擴大、腦室旁白質(zhì)容積丟失分值構(gòu)成差異有統(tǒng)計學意義(P分別為0.012和0.004)。余各單項分值構(gòu)成在兩亞組間差異無統(tǒng)計學意義。

2.4.2 足月兒組 表3顯示，MRI單項評分中分值最高的3項為腦室擴大(66分)、顱內(nèi)腦外間隙異常(63分)、腦室積膿(56分)。預后良好和預后不良亞組間腦室擴大、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)計學意義(P分別為0.002, 0.040, 0.005和0.038)。余各單項分值構(gòu)成兩亞組間差異無統(tǒng)計學意義。

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

表3 MRI單項評分與出院時預后的關(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菌性腦膜炎最常見[5,29]，后遺癥發(fā)生率高[7,8]。目前對于新生兒細菌性腦膜炎預后的研究，無論是大型回顧性隊列研究[30～32]還是特殊病原菌的個例報道[33, 34]，其中涉及到影像學表現(xiàn)的報道有限；而專注于新生兒腦膜炎影像學表現(xiàn)的研究，則多僅關(guān)注腦白質(zhì)或非腦實質(zhì)、某一征象或某一MRI技術(shù)在該病診斷和預后中的價值[9,14,25]，并未對腦膜炎腦損傷MRI表現(xiàn)類型進行全面評價。此外，上述部分研究報道中對于腦膜炎病例的選擇標準較寬泛，將細菌性腦膜炎、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納入研究，并非針對細菌性腦膜炎進行分析。因此，鑒于新生兒細菌性腦膜炎的高發(fā)病率和高致殘率，本研究按照新生兒細菌性腦膜炎的診斷標準[8]，通過嚴格的病例篩選，采用涵蓋腦白質(zhì)、腦灰質(zhì)和非腦實質(zhì)多種腦損傷表現(xiàn)的MRI評分系統(tǒng)，以期全面分析該疾病大腦損傷MRI表現(xiàn)與預后的關(guān)系。鑒于本研究為長期隨訪研究的初步結(jié)果，本文以出院時結(jié)局作為預后判斷，對早產(chǎn)兒和足月兒MRI表現(xiàn)與預后進行相關(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)病時間、MRI檢查的時間有關(guān)[16,35]，因此在進行MRI表現(xiàn)與預后關(guān)系分析中，需要首先研究這些時間因素對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后良好與不良亞組間差異有統(tǒng)計學意義，(39.1±0.9)周vs(39.8±0.6)周；兩亞組間差值為0.7周，此差異在臨床實際工作中并無臨床意義。其余時間因素的分析結(jié)果在早產(chǎn)兒和足月兒組中的預后良好和不良亞組間差異均無統(tǒng)計學意義。表明本研究中患兒出生孕周、發(fā)病時間、MRI檢查時間和發(fā)病至MRI檢查間隔時間對兩亞組的MRI評分干擾不大。

本研究結(jié)果提示新生兒細菌性腦膜炎MRI腦室擴大和腦室旁白質(zhì)容積丟失與早產(chǎn)兒出院不良結(jié)局有關(guān)(P<0.05)。而其他單項評分如顱內(nèi)腦外間隙、腦白質(zhì)非囊性信號異常、腦室積膿在早產(chǎn)兒預后良好和預后不良亞組間差異雖無統(tǒng)計學有意義(P值在0.05～0.1)，但鑒于本研究早產(chǎn)兒樣本量較小，尚無法明確這些單項評分與出院結(jié)局的關(guān)系。也有文獻報道，早產(chǎn)兒中最常見的炎癥相關(guān)性病變是腦白質(zhì)損傷，其特點為局灶性、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)學的表現(xiàn)與本研究發(fā)現(xiàn)相似。其可能的發(fā)病機制是早產(chǎn)兒血腦屏障發(fā)育不完善，某些炎性介質(zhì)更容易通過血腦屏障進入腦實質(zhì)并觸發(fā)“瀑布效應(yīng)”樣連鎖反應(yīng)而導致腦實質(zhì)損傷；早產(chǎn)兒腦成熟度低(少突膠質(zhì)細胞前體對缺血的易感性較強)、免疫系統(tǒng)不完善，致使其腦膜炎時腦白質(zhì)損傷更為明顯[1, 8]。另有研究發(fā)現(xiàn)早產(chǎn)兒斑點狀白質(zhì)病變、腦室擴大與長期預后中的智力、心理運動發(fā)育延遲，動作發(fā)育延遲以及腦癱顯著相關(guān)[36]。盡管本研究尚未總結(jié)長期預后，但出院結(jié)局顯示早產(chǎn)兒腦膜炎若出現(xiàn)MRI腦室擴大和腦室旁白質(zhì)容積丟失征象，說明出院時不良預后是存在的。

足月兒組的結(jié)果顯示腦室擴大、腦室旁白質(zhì)容積丟失、顱內(nèi)腦外間隙異常和腦室內(nèi)出血預示出院結(jié)局不良，差異有統(tǒng)計學意義(P<0.05)；而腦白質(zhì)非囊性信號異常分值構(gòu)成在兩亞組間差異非常接近有統(tǒng)計學意義(P=0.051)；余MRI單項評分在兩亞組間差異均無統(tǒng)計學意義。有文獻報道，足月兒B組鏈球菌腦膜炎可以出現(xiàn)腦室旁白質(zhì)局灶性異常信號且預后差[9]；大腸桿菌腦膜炎的足月兒可出現(xiàn)彌漫性白質(zhì)異常信號伴嚴重的腦室擴大、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)受累所導致的腦損傷與其不良預后有關(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]，可能與足月兒相對于早產(chǎn)兒而言其血腦屏障和腦膜血管發(fā)育相對成熟，作為第一屏障，更易受累有關(guān)。有文獻報道嬰兒和兒童腦膜炎MRI所見的腦膜彌散加權(quán)異常高信號預示不良預后[39]，與本文觀察到的特征相類似。這也與成人細菌性腦膜炎研究中發(fā)現(xiàn)的硬膜下積膿與出院時不良結(jié)局相關(guān)的結(jié)果一致[40]。

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

MRI綜合評分結(jié)果顯示，WMA評分高預示早產(chǎn)兒出院不良結(jié)局。WMA評分包含腦室擴大、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)非囊性信號異常。如前所述，這些單項均是早產(chǎn)兒腦白質(zhì)損傷的形態(tài)學表現(xiàn)[1]。與腦室擴大和腦室旁白質(zhì)容積丟失單項評分相比，WMA評分同樣顯示早產(chǎn)兒腦白質(zhì)損傷與預后不良相關(guān)，早產(chǎn)兒預后不良亞組WMA評分中位數(shù)高于預后良好亞組。因此采用WMA評分可以對預后判斷進行半定量分析。足月兒預后良好亞組與預后不良亞組的WMA評分中位數(shù)均為5分(正常分)，四分位區(qū)間為5～6分，顯示本研究中整個足月兒組的患兒腦白質(zhì)損傷程度輕，與出院時預后無顯著相關(guān)(P=0.603)。

MRI綜合評分中的NPA評分高預示早產(chǎn)兒和足月兒出院時不良結(jié)局。NPA包括腦室擴大、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化。在早產(chǎn)兒組單項評分中，并未發(fā)現(xiàn)顱內(nèi)腦外間隙信號異常和腦室積膿在預后良好和預后不良亞組間差異有統(tǒng)計學意義；而足月兒組單項評分中，未發(fā)現(xiàn)腦室積膿、室管膜和腦膜異常強化在預后良好和預后不良亞組間差異有統(tǒng)計學意義。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，預后不良亞組的NPA評分均高于預后良好亞組。

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

MRI形態(tài)學上腦室擴大表現(xiàn)，在新生兒腦膜炎中，既可能是腦實質(zhì)損傷后的被動擴大，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大。雖然在本文病例中沒有直接證據(jù)來說明腦室擴大直接原因，但是文獻報道腦膜炎患者腦室擴大的主要原因是炎癥累及基底池時，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，進一步加重腦積水[41]。當然也有研究認為早產(chǎn)兒腦室擴大是由于腦室旁白質(zhì)丟失而導致，因此將其歸為WMA的范疇[15,16,20]。

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

本研究不足之處：①以出院時神經(jīng)系統(tǒng)評估為結(jié)局指標，和臨床最終結(jié)局存在不同，可能會影響MRI評分在臨床的應(yīng)用價值；②樣本量局限，特別是判斷某些單項評分與預后的關(guān)系時統(tǒng)計效能不高；③由于MRI增強檢查需要增加患兒鎮(zhèn)靜時間，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，所以臨床實際工作中只有對懷疑腦膿腫的病例才進行頭顱增強MRI檢查；本研究中僅6.3%(4/63)的患兒進行了頭顱增強MRI檢查，確診腦膿腫1例，這使得本研究中對于腦膜、室管膜異常強化征象的觀察受到限制，判斷其與出院結(jié)局的關(guān)系時會存在局限。

[1]Strunk T, Inder T, Wang X, et al. Infection-induced inflammation and cerebral injury in preterm infants. Lancet Infect Dis, 2014, 14(8): 751-762

[2]Counsell SJ, Tranter SL, Rutherford MA. Magnetic resonance imaging of brain injury in the high-risk term infant. Semin Perinatol, 2010, 34(1): 67-78

[3]Bonifacio SL, Glass HC, Peloquin S, et al. A new neurological focus in neonatal intensive care. Nat Rev Neurol, 2011, 7(9): 485-494

[4]Hagberg H, Gressens P, Mallard C. Inflammation during fetal and neonatal life: implications for neurologic and neuropsychiatric disease in children and adults. Ann Neurol, 2012, 71(4): 444-457

[5]Holt DE, Halket S, de Louvois J, et al. Neonatal meningitis in England and Wales: 10 years on. Arch Dis Child Fetal Neonatal Ed,2001, 84(2): F85-F89

[6]Gaschignard J, Levy C, Romain O, et al. Neonatal Bacterial Meningitis: 444 Cases in 7 Years. Pediatr Infect Dis J, 2011, 30(3): 212-217

[7]Stevens JP, Eames M, Kent A, et al. Long term outcome of neonatal meningitis. Arch Dis Child Fetal Neonatal Ed, 2003, 88(3): F179-F184

[8]邵肖梅, 葉鴻瑁, 丘小汕. 實用新生兒學. 第4版. 北京: 人民衛(wèi)生出版社, 2011: 347-351

[9]Hernandez MI, Sandoval CC, Tapia JL, et al. Stroke patterns in neonatal group B streptococcal meningitis. Pediatr Neurol, 2011, 44(4): 282-288

[10]Malik GK, Trivedi R, Gupta A, et al. Quantitative DTI assessment of periventricular white matter changes in neonatal meningitis. Brain Dev, 2008, 30(5): 334-341

[11]Rollins NK, Morriss MC, Evans D, et al. The role of early MR in the evaluation of the term infant with seizures. Am J Neuroradiol, 1994, 15(2): 239-248

[12]Jan W, Zimmerman RA, Bilaniuk LT, et al. Diffusion-weighted imaging in acute bacterial meningitis in infancy. Neuroradiology, 2003, 45(9): 634-639

[13]Mader I, Schoning M, Klose U, et al. Neonatal cerebral infarction diagnosed by diffusion-weighted MRI: pseudonormalization occurs early. Stroke, 2002, 33(4): 1142-1145

[14]Malik GK, Yadav A, Trivedi R, et al. Temporal alterations in brain water diffusivity in neonatal meningitis. Acta Paediatr, 2009, 98(9): 1426-1432

[15]Miller SP, Cozzio CC, Goldstein RB, et al. Comparing the diagnosis of white matter injury in premature newborns with serial MR imaging and transfontanel ultrasonography findings. Am J Neuroradiol, 2003, 24(8): 1661-1669

[16]Miller SP, Ferriero DM, Leonard C, et al. Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J Pediatr, 2005, 147(5): 609-616

[17]Roine I, Weisstaub G, Peltola H. Influence of malnutrition on the course of childhood bacterial meningitis. Pediatr Infect Dis J, 2010, 29(2): 122-125

[18]Fluegge K, Siedler A, Heinrich B, et al. Incidence and clinical presentation of invasive neonatal group B streptococcal infections in Germany. Pediatrics, 2006, 117(6): e1139-e1145

[19]Levent F, Baker CJ, Rench MA, et al. Early outcomes of group B streptococcal meningitis in the 21st century. Pediatr Infect Dis J, 2010, 29(11): 1009-1012

[20]Woodward LJ, Anderson PJ, Austin NC, et al. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med, 2006, 355(7): 685-694

[21]Shroff MM, Soares-Fernandes JP, Whyte H, et al. MR imaging for diagnostic evaluation of encephalopathy in the newborn. Radiographics, 2010, 30(3): 763-780

[22]Inder TE, Wells SJ, Mogridge NB, et al. Defining the nature of the cerebral abnormalities in the premature infant: a qualitative magnetic resonance imaging study. J Pediatr,2003, 143(2): 171-179

[23]Wong AM, Zimmerman RA, Simon EM, et al. Diffusion-weighted MR imaging of subdural empyemas in children. AJNR Am J Neuroradiol, 2004, 25(6): 1016-1021

[24]Tsuchiya K, Osawa A, Katase S, et al. Diffusion-weighted MRI of subdural and epidural empyemas. Neuroradiology, 2003, 45(4): 220-223

[25]Han KT, Choi DS, Ryoo JW, et al. Diffusion-weighted MR imaging of pyogenic intraventricular empyema. Neuroradiology, 2007, 49(10): 813-818

[26]Mohan S, Jain KK, Arabi M, et al. Imaging of meningitis and ventriculitis. Neuroimaging Clin N Am, 2012, 22(4): 557-583

[27]Papile LA, Burstein J, Burstein R, et al. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr, 1978, 92(4): 529-534

[28]Jansson AK, Enblad P, Sjolin J. Efficacy and safety of cefotaxime in combination with metronidazole for empirical treatment of brain abscess in clinical practice: a retrospective study of 66 consecutive cases. Eur J Clin Microbiol Infect Dis, 2004, 23(1): 7-14

[29]Jaremko JL, Moon AS, Kumbla S. Patterns of complications of neonatal and infant meningitis on MRI by organism: a 10 year review. Eur J Radiol, 2011, 80(3): 821-827

[30]Okike IO, Johnson AP, Henderson K L, et al. Incidence,etiology, and outcome of bacterial meningitis in infants aged <90 days in the United Kingdom and Republic of Ireland: prospective, enhanced, national population-based surveillance. Clin Infect Dis, 2014, 59(10): e150-e157

[31]Lin MC, Chi H, Chiu NC, et al. Factors for poor prognosis of neonatal bacterial meningitis in a medical center in Northern Taiwan. J Microbiol Immunol Infect, 2012, 45(6): 442-447

[32]de Louvois J, Halket S, Harvey D. Neonatal meningitis in England and Wales: sequelae at 5 years of age. Eur J Pediatr,2005, 164(12): 730-734

[33]Vaz MC, Ferreira M, Ferreira MM, et al. Sepsis, meningitis and cerebral abscesses caused by Citrobacter koseri. BMJ Case Rep, 2012

[34]Sonntag J, Kaczmarek D, Brinkmann G, et al. Complicating neonatal Escherichia coli meningitis. Z Geburtshilfe Neonatol, 2004, 208(1): 32-35

[35]Zhang J(張靜)，Mao J, Li J, et al. MRI findings of neonatal purulent meningitis caused by different pathogenic bacteria. Chin J Contemp Pediatr(中國當代兒科雜志), 2012,14(7): 489-495

[36]de Bruine FT, van den Berg-Huysmans AA, Leijser LM, et al. Clinical implications of MR imaging findings in the white matter in very preterm infants: a 2-year follow-up study. Radiology, 2011, 261(3): 899-906

[37]Shah DK, Daley AJ, Hunt RW, et al. Cerebral white matter injury in the newborn following Escherichia coli meningitis. Eur J Paediatr Neurol, 2005, 9(1): 13-17

[38]Oliveira CR, Morriss MC, Mistrot JG, et al. Brain magnetic resonance imaging of infants with bacterial meningitis. J Pediatr, 2014, 165(1): 134-139

[39]Kawaguchi T, Sakurai K, Hara M, et al. Clinico-radiological features of subarachnoid hyperintensity on diffusion-weighted images in patients with meningitis. Clin Radiol, 2012, 67(4): 306-312

[40]Jim KK, Brouwer MC, van der Ende A, et al. Subdural empyema in bacterial meningitis. Neurology, 2012, 79(21): 2133-2139

[41]Chatterjee S, Chatterjee U. Overview of post-infective hydrocephalus. Childs Nerv Syst, 2011, 27(10): 1693-1698

(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

復旦大學附屬兒科醫(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)