中樞神經(jīng)系統(tǒng)感染簡介

1、中樞神經(jīng)系統(tǒng)感染 INFECTIONS OF THE CENTRAL NERVOUS SYSTEM,Neurology Department The Second Hospital of Harbin Medical University,第一節(jié) 概述,Term：Infections of CNS All kinds of pathogen (bacteia,viruses,spirochete ,parasites,fungi,rickettsia and prion prottein) invade cerebral parenchyma, meninges and blood vesse

2、l lead to acute and subacute infections,第一節(jié) 概述,分類： 感染的部位 ；發(fā)病情況及病程 ；特異性致病因子 CNS感染途徑(pathway of infection) hematogenous spread； direct infection ； Peripheral nerves pathway CNS病毒感染性疾病新的認(rèn)識,第二節(jié) 病毒感染性疾病 Viral infections of CNS,單純皰疹病毒性腦炎 Herpes Simplex Encephalitis Creutzfeldt-Jakob Disease,Herpes Simplex

3、 Encephalitis,病因及發(fā)病機制( Causes and Mechanisms) 病理（pathology) 臨床表現(xiàn) (Clinical features) 輔助檢查 (laboratory finding) 診斷及鑒別診斷 (Diagnosis and Differential Diagnosis) 治療（treatment,HSE-Causes and Mechanisms,HSV-嗜神經(jīng)(neurotropic )DNA病毒 90%的人類HSE是由I型引起 70%HSE起因于內(nèi)源性病毒的活化 (復(fù)發(fā)性皰疹感染 ) 25%的病例是原發(fā)感染 (口腔和呼吸道 ) 6%15%系由II

4、型所致 (產(chǎn)婦生殖道HSV-II原發(fā)感染 ) 絕大多數(shù)新生兒的HSE系HSV-II引起,HSE- Pathology,顳葉、額葉等部位出血性壞死 |、滲出 急性期后可見小膠質(zhì)細(xì)胞增生 Intense hemorrhagic necrosis of the inferior and medial parts of the temporal lobes and the medial-orbital parts of the frontal lobes,HSE-Pathology,Cowdry A型包涵體 (A type inclusion body)存在于病灶邊緣的部分神經(jīng)細(xì)胞核內(nèi) 及星型細(xì)胞和少

5、突膠質(zhì)細(xì)胞核內(nèi),HSE- Clinical feature,1任何年齡、季節(jié)均可發(fā)病原發(fā)感染的潛伏期為221天，平均6天；前驅(qū)期癥狀 2病程 多急性起病 ，口唇皰疹史 （1/4），高熱，首發(fā)癥狀 ：頭痛、輕微的意識和人格改變 或全身性或部分性運動性發(fā)作 ；病情緩慢進展精神癥狀表現(xiàn)突出智能障礙也較明顯 3 神經(jīng)癥狀 局灶性腦損害 ；腦膜刺激征 ；意識障礙 ；全身性或部分性癲癇 。重癥腦疝形成而死亡 （死亡率高達40%70,HSE-Clinical feature,1.It occurs sporadically throughout the year and in patients of all

6、 ages. During prodromal stage:fever,headache,muscular ache etc. 2.The onset is acute,patients may had herpes labialis(1/4) and fever.The early manifestations:headach,personality change,slight concious disorder and seizures .Psychotic behavior, memory loss become evident later,HSE-Clinical feature,3.

7、Neurologic symptom and sign hemiparesis,aphasia,meningeal rritatioin,disorder of conciousness,focal or generalized seizures.It may result in coma or death in some cases,HSE- Laboratory Diagnosis,1腦電圖 彌漫性高波幅慢波 2頭顱CT可正常，也可見一側(cè)或雙側(cè)顳葉、海馬及邊緣系統(tǒng)局灶性低密度區(qū) 3腦脊液檢查壓力及細(xì)胞數(shù)正?；蜉p度增高，重癥者可明顯增高。 4腦脊液病原學(xué)檢查對診斷頗有意義 檢測HSV抗原 檢

8、測HSV特異性lgM、lgG抗體 CSF中HSV-DNA（PCR快速診斷） 腦組織病理學(xué)及病原學(xué)檢查,HSE-Laboratory Diagnosis,EEG:lateralized high-voltage slow-waves. CT scans show hypodensity of the affected areas. MRI shows signal changes in almost all. 圖1 圖2 圖3 CSF: increased pressure, lymphocytic pleocytosis, mild protein elevation and normal g

9、lucose,HSE-Laboratory Diagnosis,Tests for the detection of HSV antigen in the CSF by the application of PCR are useful. The absolute way for dianosis:fluorecent antibody study and viral cultrue of cerebral tissue obtained by brain biopsy,HSE-diagnosis,1臨床診斷依據(jù)：口唇或生殖道皰疹史；高熱、腦炎、精神癥狀三主征及局灶性神經(jīng)系統(tǒng)損害體征；腦脊液紅

10、、白細(xì)胞數(shù)增多，糖和氯化物正常；腦電圖以顳、額區(qū)損害為主的腦彌漫性異常；頭顱CT或MRI發(fā)現(xiàn)顳葉局灶性出血性腦軟化灶；特異性抗病毒藥物治療有效。 2. 實驗室檢查 ：CSF病原體檢查及病理檢查,HSEDifferential diagnosis,急性播散性腦脊髓炎：多在感染或疫苗接種后急性發(fā)病 結(jié)核性腦膜腦炎：結(jié)核病病史或接觸史，慢性過程，腦膜刺激征是TBM早期表現(xiàn) ，可有腦神經(jīng)損害，CSF檢查提示診斷 。 腸道病毒性腦炎：也是病毒性腦炎的常見病因之一，多見于夏秋季，可為流行性或散發(fā)性 帶狀皰疹病毒性腦炎,HSE -treatment,Antiviral agents There was no

11、 specific treatment for HVE untill the late 1970s acyclovir was introduced. Acyclovir and ganciclovir are most effective drugs.They significantly reduce both the mortality and morbidity,HSE- treatment,1抗病毒化學(xué)藥物治療 (1) 無環(huán)鳥苷 (阿昔洛韋, acyclovir) (2) 更昔洛韋(ganciclovir) 2免疫治療 干擾素及其誘生劑 轉(zhuǎn)移因子 腎上腺皮質(zhì)激素 3全身支持治療 4對癥

12、治療,Creutzfeldt-Jakob Disease,Creutzfeldt-Jakob病 (CJD)是最常見的人類朊蛋白病 （具傳染性的朊蛋白所致的散發(fā)性中樞神經(jīng)系統(tǒng)變性疾?。?CJD is also called Subacute Spongiform Encephalopathy. (SSE) It belongs to the category called the transmissible spongiform encephalopathies (prion diseases,PrP and prion Protein dease,朊蛋白(prion protein, PrP)

13、一種既具有傳染性又缺乏核酸的非病毒性致病因子 Prion is neither a virus nor a viroid(nucleic acid alone,without a capsid structure)but the conversion of a normal cellular protein,PrP and prion Protein dease,人類朊蛋白病還有 Kuru病、Gerstmann-Straussler綜合征(GSS)、致死性家族性失眠癥(FFI)、缺乏特征性病理改變的朊蛋白癡呆和伴痙攣性截癱的朊蛋白癡呆,What is CJD,Refer to a distin

14、ctive cerebral disease in which a rapidly progressive and profound dementia associated with cerebellar ataxia,diffuse myoclonic jerks and a variety of other visual and neurologic abnormalities. The outstanding features of the neuropathologic changes are widespread neuronal loss and gliosis accompani

15、ed by a striking vacuolation or spongy state of the affected regions,CJD- Pathogenesis and Type,1型和2型存在于散發(fā)性CJD(sporadicula CJD ) 3型為醫(yī)源性CJD-通過角膜、硬腦膜移植，腦源性生物制品和埋藏未充分消毒的腦電極而傳播 Type-3:iatrogenic CJD by transplantation of corneas and implantation of infected depth electrdes etc,CJD- Pathogenesis,4型是新變異型-

16、與瘋牛病(MCD)具有相似的種系特異性 PrP基因突變形成遺傳性家族型CJD,CJD- Pathology,大體-腦呈海綿狀改變，皮質(zhì)、基底節(jié)和脊髓萎縮變性。 Spongy appearance shows in cerebral and cerebellar cortex,CJD -Pathology,顯微鏡下-神經(jīng)元丟失、星形細(xì)胞增生、細(xì)胞胞漿中空泡形成，可發(fā)現(xiàn)感染組織內(nèi)異常PrP淀粉樣斑塊。 Widespread neuronal loss and gliosis accompanied by a striking vacuolation and PrPsc in the affecte

17、d regions,CJD-臨床表現(xiàn),1發(fā)病年齡2578歲，平均58歲，男女均可罹患，新變異型平均26歲 2隱襲起病，緩慢進行性發(fā)展 初期：表現(xiàn)頗似神經(jīng)癥，可有頭痛、眩暈、共濟失調(diào)及視覺障 礙等 中期：進行性癡呆為主要表現(xiàn)，伴人格改變 ，有失語、偏癱、錐體束征 或肌肉萎縮 及2/3病人出現(xiàn)肌陣攣，最具特征性 晚期：出現(xiàn)尿失禁、無動性緘默、昏迷 等 3變異型CJD臨床表現(xiàn)共濟失調(diào)和行為改變,CJD-clinical feature,1. It occurs mostly in the late middle age, although can occur in young adult. 2. P

18、rogressive development. The early stage: Atypical The mid stage: gradual dementia with personality change. Myoclonus occurs in 2/3 of patients. The late stage : Coma, akinetic mutism. 3. Variant CJD,CJD- Laboratory Finding,1免疫熒光檢測CSF中14-3-3蛋白可呈陽性 -可疑CJD病人重要指標(biāo)。血清S100蛋白（隨病情進展呈持續(xù)性增高）。 2腦電圖：疾病中晚期可出現(xiàn)間隔0.

19、52秒周期性棘-慢復(fù)合波。 3晚期CT和MRI：可見腦萎縮；MRI顯示雙側(cè)尾狀核、殼核T2呈對稱性均質(zhì)高信號 ，T1可完全正常,CJD-Laboratory Finding,Test of CSF by immunoassay, the finding of 14-3-3 protein is very useful in separating SSE. Also is the serum P-100. EEG :High voltage slow and sharp-wave complexes(0.5-2Hz). MRI subtle hyperintensity of the lenti

20、cular nuclei on T2 weighted images when the disease is fully established,CJD- Diagnosis(診斷標(biāo)準(zhǔn),很可能(probable) CJD 在2年內(nèi)發(fā)生的進行性癡呆； 肌陣攣、視力障礙、小腦癥狀、無動性緘默等四項中具有其中兩項； 腦電圖周期性同步放電的特征性改變。 如病人腦活檢發(fā)現(xiàn)海綿狀態(tài)和PrPSC者，則為確診的CJD。 可用腦蛋白檢測代替腦電圖特異性改變,CJD-Diagnosis,Probable SSE 1)Progressive dementia in 2 years 2)Two of myoclonu

21、s, visual disterbance, ataxia and akinetic mutism. 3)EEG: synchronous discharge. Definite diagnosis Spongy or PRPsc is found by brain tissue biopsy,CJD-鑒別診斷,Alzheimer病 進行性核上性麻痹 橄欖腦橋小腦萎縮 腦囊蟲病 肌陣攣性癲等鑒別,CJD-治療及預(yù)后,尚無有效治療 對癥治療 巴氯芬(baclofen)治療痙攣性張力增高， 氯硝西泮治療肌陣攣， 癡呆可用三樂喜、哌醋甲酯(利他林)和尼麥角林(腦通)等。 應(yīng)用反義寡核苷酸或基因治療可

22、能達到治療目的 90%病例于病后1年內(nèi)死亡,腦囊蟲病,Cerebral Cysticercosis,Cerebral Cysticercosis,由豬帶絳蟲蚴蟲(囊尾蚴)寄生腦組織形成包囊所致。 Cysticercosis is the larval stage (cysticercus) of infection with the pork tapeworm,Cerebral Cysticercosis,是一種最常見的CNS寄生蟲感染，也是我國北方癥狀性癲常見的病因之一。 Cysticercosis is a leading cause of epilepsy and other neuro

23、logic disturbances,腦囊蟲病-病因及發(fā)病機制,最常見的傳播途徑是攝入帶有蟲卵污染的食物 少見原因為肛門-口腔轉(zhuǎn)移而形成的自身感染或者是絳蟲的節(jié)片逆行入胃 蟲卵進入十二指腸內(nèi)孵化逸出六鉤蚴，蚴蟲經(jīng)血液循環(huán)分布全身并發(fā)育成囊尾蚴，有不少囊尾蚴寄生在腦內(nèi),腦囊蟲病- Pathology,典型的包囊大小為510mm，可有薄壁包膜，或呈多個囊腔 The cysts may be 5-10mm.The lesions are most often multiple but may be solitary,Cysticercosis -Pathology,腦實質(zhì)中包囊內(nèi)存活的蚴蟲很少引起炎

24、癥，通常在感染后數(shù)年蚴蟲死亡后才出現(xiàn)明顯的炎癥反應(yīng) Only when the cyst degenerated many months or years after the initial infestation, an inflammatory and granulomatous reaction is elicited and focal symptoms arise,腦囊蟲病- Clinical Feature,1腦實質(zhì)型 臨床癥狀與包囊的位置有關(guān) 。 2蛛網(wǎng)膜型 頭痛、腦積水和虛性腦膜炎等。 3腦室型 阻塞性腦積水；布龍(Brun)征發(fā)作（移動的包囊，可突然阻塞第四腦室正中孔，導(dǎo)致腦

25、壓突然增高，引起眩暈、嘔吐、意識障礙和跌倒 ） 。 4脊髓型 非常罕見,Clinical Feature,The cerebral manifestations of cysticercosis are diverse, related to the encystment and subsequent calcification of the larvae in cerebral parenchyma, subarachnoid space and ventricle. The flow of CSF may be obstructed by large subarachnoid or intraventricular cyst and leads to obstructive hydrocephalus,腦囊蟲病- Laboratory Diagnosis,1血常規(guī)檢查嗜酸性粒細(xì)胞增多。 2用ELISA和Western 印跡法檢測血清囊蟲抗體常為陽性。 3頭顱CT和MRI可發(fā)現(xiàn)腦積水及被阻塞的部位，CT可見單個或多個鈣化點，CT平掃見包囊