陳文雄 楊思達 高媛媛 周艷霞 劉鴻圣 彭炳蔚 王秀英 麥堅凝 陶建平 寧書堯 鐘燕銀

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·論著·

陳文雄1楊思達1高媛媛1周艷霞1劉鴻圣2彭炳蔚1王秀英1麥堅凝1陶建平3寧書堯1鐘燕銀1

1 方法

1.1 重癥病毒性腦炎診斷標(biāo)準(zhǔn) 參照《諸福棠實用兒科學(xué)》兒童病毒性腦炎診斷標(biāo)準(zhǔn)[6]，符合以下條件之一為重癥病毒性腦炎[7]：①頻繁抽搐或驚厥持續(xù)狀態(tài)；②稽留高熱；③不同程度意識障礙；④腦干顱神經(jīng)損害；⑤顱內(nèi)高壓癥、腦疝形成；⑥多臟器功能衰竭。

1.3 研究對象納入標(biāo)準(zhǔn) 檢索我院神經(jīng)內(nèi)科2012年6月至2014年9月電子病案系統(tǒng)，符合重癥病毒性腦炎和NCSE診斷的病例進入本文分析。

1.4 VEEG監(jiān)測方法 我院VEEG監(jiān)測采用美國Nicolet公司Nicolet-one 32通道視頻腦電圖儀，按照國際10-20系統(tǒng)標(biāo)準(zhǔn)安放19個頭皮記錄電極，記錄患兒發(fā)作期及發(fā)作間期VEEG；昏迷患兒持續(xù)或間斷密集VEEG監(jiān)測7 d，之后1～2周定期復(fù)查VEEG；非昏迷患兒均行至少1次VEEG監(jiān)測，連續(xù)記錄最少1 h，1～2周定期復(fù)查VEEG；結(jié)果由神經(jīng)內(nèi)科及腦電圖醫(yī)生結(jié)合腦電記錄分析，按統(tǒng)一標(biāo)準(zhǔn)判定；監(jiān)測過程中予地西泮0.3 mg·kg-1靜脈注射，每次最大劑量<10 mg，以1～2 mg·min-1均勻注入。節(jié)律性異常腦電波減少或消失，同時伴臨床征象好轉(zhuǎn)為藥物起效的標(biāo)準(zhǔn)。

表1 NCSE的臨床標(biāo)準(zhǔn)[9]

注 以上標(biāo)準(zhǔn)改良自Kaplan(2007)[12]。1)樣放電：棘波，多棘波，尖波、尖慢綜合波；2)若EEG改善而臨床表現(xiàn)無改善，或波動無確定演化，應(yīng)考慮NCSE可能；3)具發(fā)作頻率、波幅及分布的演化現(xiàn)象：起始遞增(波幅增加與頻率改變)，或模式演化(頻率改變>1 Hz或分布改變)，或終末遞減(波幅或頻率)。

2 結(jié)果

2.1 一般資料 9例重癥病毒性腦炎NCSE連續(xù)病例進入本文分析，男5例，女4例。腦炎起病年齡(7.2±3.9)歲，入院時Glasgow評分(8.6±1.9)分，腦炎起始與NCSE起始間隔4～70(19.4±20.9)d。

2.2 臨床特征(表2)

2.2.1 病因分析 9例CSF病原學(xué)(單純皰疹病毒、巨細胞病毒、肺炎支原體、腸道病毒、EB病毒)檢測未發(fā)現(xiàn)明確病原，其中例2感染腮腺炎，例6合并驚厥，在調(diào)整AEDs期間出現(xiàn)NCSE。

2.2.2 NCSE類型 SEC 4例(例1～4)，CPSE 4例(例5～8)，不典型ASE 1例(例9)。

圖1 例7EEG表現(xiàn)

Fig 1 EEG findings of case 7

Notes Male, 1 y 2 m. A: eyes-open state of mutism with upward look of both eyes; recording parameters: bilateral ear referential montage, paper speed 3 cm·s-1, high frequency 70 Hz, low frequency 0.5 Hz; ictal VEEG: background electrical activity slow, spike rhythm at left frontal pole & frontal area; B: the behaviors of cry with upward look of both eyes were reduced after 2 min of intravenous administration of diazepam; recording parameters: bilateral ear referencial montage, paper speed 3 cm·s-1, high frequency 70 Hz, low frequency 0.5 Hz; VEEG after 2.2 min of intravenous administration of diazepam: the fast wave at frontal area disappeared with the background of 2-3 Hz moderate low amplitude delta rhythm

2.4 臨床發(fā)現(xiàn) 4例SEC患兒臨床發(fā)現(xiàn)包括昏迷、昏睡、躁動、肢體或嘴角微小抽動、輕微眨眼或眼震和嘴角咂動等；4例CPSE患兒臨床發(fā)現(xiàn)包括認(rèn)知倒退、不能認(rèn)人、不清醒、混亂、躁狂、眨眼、嘴角輕微抽動、睜眼緘默、斜視和手摸索等，其中例6在AEDs減量調(diào)整過程中出現(xiàn)孤獨癥樣行為(叫名不理、眼神回避、刻板樣重復(fù)行為等)；例9不典型ASE患兒表現(xiàn)為不清醒、混亂、嘴角輕微抽動及流涎。

2.5 MRI 9例病毒性腦炎急性期均行頭顱MRI檢查，均有不同程度異常發(fā)現(xiàn)，以腦實質(zhì)或腦膜局灶、多局灶、彌漫性損害為特點(圖2)。6例患兒雙側(cè)大腦皮質(zhì)彌漫性腫脹并異常信號(2例累及基底節(jié))，例6累及小腦，例5累及背側(cè)丘腦，例8累及軟腦膜(表 2)。

圖2 例7MRI所見

Fig 2 Cerebral MRI findings of case 7

Notes Case 7, male, 1 y 2 m. A: Brain MRI (acute phase): Bilateral cerebral hemisphere and basal ganglia swellen; T2WI and T2WI FLAIR: signal diffuse increased slightly; T1WI signal did not change significantly; Contrast-enhanced scan: The shadow of enhanced small blood vessels on the surface of bilateral cerebral hemisphere increased

2.6 治療、預(yù)后與隨訪 4例SEC患兒予咪達唑侖聯(lián)合多種AEDs(丙戊酸鈉、左乙拉西坦、苯妥英鈉、氯硝西泮)治療；4例CPSE和1例不典型ASE患兒予丙戊酸鈉、左乙拉西坦和氯硝西泮等治療。例5自動出院，余8例NCSE持續(xù)(39.8±39.2)d，其中4例SEC患兒NCSE持續(xù)(42.8±21.8)d；3例非SEC患兒(例7～9)NCSE持續(xù)(9.0±1.7)d，例6 NCSE持續(xù)4個月。

3例復(fù)查MRI提示遺留輕度異常：雙側(cè)大腦半球腦溝加深，幕上腦室稍豐滿(例1、3)、雙側(cè)小腦半球腦溝稍加深(例6)；例2和4遺留彌漫性慢性缺損；例7和8提示亞急性局灶缺損。

3 討論

本文9例前驅(qū)均有驚厥發(fā)作。Tay等[14]報道12/19例患兒存在前驅(qū)驚厥發(fā)作。晚近有研究[7]報道前驅(qū)驚厥發(fā)作可增加34%發(fā)生NCSE的可能；本文3例前驅(qū)尚有CSE發(fā)生。Tay等[14]也報道5/19例患兒前驅(qū)發(fā)生CSE。張赟健等[17]報道2例NCSE患兒前驅(qū)有CSE發(fā)生。汪葉松等[17]監(jiān)測17例CSE發(fā)作后成人患者，4例診斷為NCSE。Feen等[18]建議CSE發(fā)作停止后伴意識改變>20 min者，均需行VEEG監(jiān)測。

3.2 重癥病毒性腦炎患兒NCSE的臨床發(fā)現(xiàn) Kaplan等[19]將非驚厥發(fā)作臨床表現(xiàn)歸納為興奮性與抑制性癥狀。本文發(fā)現(xiàn)重癥病毒性腦炎患兒非驚厥發(fā)作既有興奮性，亦有抑制性癥狀，表現(xiàn)多樣，包括昏迷、躁動、眨眼或眼震、肢體或口面部微小抽動、認(rèn)知障礙、孤獨癥樣行為、自動癥及睜眼緘默等。汪葉松等[17]及申浩等[20]也報道重癥或昏迷成人患者NCSE臨床表現(xiàn)存在口、眼或肢體微小抽動，混亂、譫妄等精神癥狀，或僅有昏睡狀態(tài)。新近的NCSE臨床標(biāo)準(zhǔn)[9]提示，覺察臨床細微的發(fā)作現(xiàn)象，如眨眼、肢體或口面部的微小抽動等，也是支持NCSE診斷的依據(jù)之一。

3.3 重癥病毒性腦炎患兒NCSE的MRI表現(xiàn) 本文9例病毒性腦炎急性期均有不同程度頭顱MRI異常發(fā)現(xiàn),以雙側(cè)大腦皮質(zhì)廣泛性損害為主，可能直接或間接與EEG異常放電的起源部位相關(guān)，提示頭顱神經(jīng)影像學(xué)腦炎急性期異?？赡苁荖CSE發(fā)生的潛在危險因素。Greiner等[7]報道急性皮質(zhì)神經(jīng)影像學(xué)異常增加了29%發(fā)生NCSE的可能，如驚厥與急性皮質(zhì)神經(jīng)影像學(xué)異常同時出現(xiàn)，則發(fā)生NCSE的可能性增至82%。

本文發(fā)現(xiàn)重癥病毒性腦炎患兒初始Glasgow評分、MRI累及范圍與預(yù)后可能相關(guān)。例2、4和9 Glasgow評分低，頭顱MRI顯示廣泛性損害，預(yù)后較差；例1、3和6 Glasgow評分高，頭顱MRI輕度異常的患兒預(yù)后相對較好。

NCSE對神經(jīng)系統(tǒng)的影響尚不明確[5]。新近研究報道NCSE是創(chuàng)傷后大腦損傷患者腦萎縮的一個獨立危險因素[28]。NCSE患兒死亡與潛在的驚厥原因相關(guān)，而非NCSE持續(xù)時間或是否出現(xiàn)NCSE[5]。當(dāng)前證據(jù)表明臨床癥狀改善至少在一定程度上與及時、有效的抗驚厥治療相關(guān)[29]。因此，關(guān)注重癥顱內(nèi)感染患兒原發(fā)病治療同時，不能忽視NCSE治療。

本文的不足之處和局限性：①病毒性腦炎患兒多存在認(rèn)知障礙伴不自主動作，較難與NCSE發(fā)作相鑒別，NCSE的實際病程可能更長； ②每1～2周隨訪EEG，可能影響對NCSE病例評估的準(zhǔn)確性。

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(本文編輯：丁俊杰)

Analysis of non-convulsive status epilepticus in 9 children with severe viral encephalitis

CHENWen-xiong1,YANGSi-da1,GAOYuan-yuan1,ZHOUYan-xia1,LIUHong-sheng2,PENGBing-wei1,WANGXiu-ying1,MAIJian-ning1,TAOJian-ping3,NINGShu-yao1,ZHONGYan-yin1

(1DepartmentofNeurology;2DepartmentofMagneticResonance;3DepartmentofPediatricIntensiveCareUnit,GuangzhouWomenandChildren′sMedicalCenter,Guangzhou510623,China)

CHEN Wen-xiong，E-mail:chenwx100@hotmail.com

ObjectiveTo explore the clinical features, diagnosis and treatment of non-convulsive status epilepticus (NCSE) in children with severe viral encephalitis.MethodsThe clinical manifestations, video electroencephalographic (VEEG) features, anti-epilepsy treatment and prognosis of NCSE in children with severe viral encephalitis in the child neurological inpatient setting of Guangzhou Women and Children′s Medical Center between June 2012 and September 2014 were retrospectively analyzed. Results Nine patients including 5 boys were identified. The age onset of encephalitis was (7.2±3.9) years. The Glasgow scores of 9 patients were (8.6±1.9) points. The average interval between the onset of encephalitis and NCSE ranged from 4 to 70 (19.4±20.9) days. NCSE types included status epilepticus in coma (SEC) (n=4), complex partial status epilepticus (n=4), and atypical absence status epilepticus (n=1). Eight children were with severe viral encephalitis and 1 child with severe viral encephalitis in changing antiepileptic drug regimen. The preceding seizures in all children and convulsive status epilepticus in 3 patients were found. A variety of clinical manifestations, including limb or mouth and face tiny tic, eye blinking or nystagmus, cognitive impairment, autistic-like behavior, mutism with eye open and automatism were observed. The characteristics of ictal VEEG generally included slow activity of background; focal, multi-focal, or generalized δ, θ , β，spike rhythmic activity, or continuous spike and wave discharges; with the evolution of frequency, amplitude, and distribution; frequently of frontal or occipital lobe origin. The patients diagnosed as SEC were treated with general anesthesia (midazolam) plus multiple antiepileptic drug (AEDs) with average duration of attack of 42.8 days, whereas others with non-SEC were provided with multiple AEDs with average duration of attack of 9 days in 3 cases and 4 months in 1 case with changing AEDs regimen respectively. Among 9 patients, 1 failed to be followed up, 1 died, and 7 were followed up for 3 months to 2.5 years. Six patients had different degree abnormalities of ictal or interictal VEEG, though 1 case with normal VEEG outcome. One patient had normal neurological function, whereas other 6 patients had symptomatic epilepsy with different degree abnormalities of cognition in 5 patients and persistent vegetative state in one patient respectively.ConclusionClinical manifestations of NCSE in children with severe viral encephalitis may present with mouth, face and limb movement phenomena, cognitive and behavioral changes. The morphologies of ictal VEEG are various, in which the spike rhythmic activity may serve as a unique pattern. The measures of treatment and effective time are associated with NCSE types.

Nonconvulsive status epilepticus; Severe viral encephalitis; Video electroencephalography; Children

廣州市婦女兒童醫(yī)療中心 1 神經(jīng)內(nèi)科；2 磁共振室；3 兒科重癥監(jiān)護室 廣州，510623

陳文雄，E-mail:chenwx100@hotmail.com

10.3969/j.issn.1673-5501.2015.04.008

2015-04-30

2015-07-15)