中樞神經(jīng)系統(tǒng)感染

中樞神經(jīng)系統(tǒng)感染

INFECTIONSOFTHECENTRALNERVOUSSYSTEM

NeurologyDepartmentTheSecondHospitalofHarbinMedicalUniversity第一節(jié)概述

Term：InfectionsofCNS

Allkindsofpathogen(bacteia,viruses,spirochete,parasites,fungi,rickettsiaandprionprottein) invadecerebralparenchyma,meningesandbloodvesselleadtoacuteandsubacuteinfections.第一節(jié)概述分類：感染的部位；發(fā)病狀況及病程；特異性致病因子CNS感染途徑(pathwayofinfection)①hematogenousspread；②directinfection；③PeripheralnervespathwayCNS病毒感染性疾病新的認(rèn)識第二節(jié)病毒感染性疾病

ViralinfectionsofCNS單純皰疹病毒性腦炎HerpesSimplexEncephalitis

Creutzfeldt-JakobDiseaseHerpesSimplexEncephalitis

病因及發(fā)病機(jī)制(CausesandMechanisms)病理（pathology)臨床體現(xiàn)(Clinicalfeatures)輔助檢查(laboratoryfinding)診療及鑒別診療(DiagnosisandDifferentialDiagnosis)治療（treatment)

HSE--CausesandMechanismsHSV-嗜神經(jīng)(neurotropic)DNA病毒90%的人類HSE是由I型引發(fā)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引發(fā)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 Intensehemorrhagicnecrosisoftheinferiorandmedialpartsofthetemporallobesandthemedial-orbitalpartsofthefrontallobes.HSE-PathologyCowdryA型包涵體(Atypeinclusionbody)存在于病灶邊沿的部分神經(jīng)細(xì)胞核內(nèi)及星型細(xì)胞和少突膠質(zhì)細(xì)胞核內(nèi)。

HSE--Clinicalfeature1．任何年紀(jì)、季節(jié)均可發(fā)病原發(fā)感染的潛伏期為2~21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、輕微的意識和人格變化或全身性或部分性運(yùn)動(dòng)性發(fā)作；病情緩慢進(jìn)展精神癥狀體現(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(dá)40%~70%）。HSE-Clinicalfeature1.Itoccurssporadicallythroughoutthe

yearandinpatientsofallages.Duringprodromalstage:fever,headache,muscularacheetc.2.Theonsetisacute,patientsmayhadherpeslabialis(1/4)andfever.Theearlymanifestations:headach,personalitychange,slightconciousdisorderandseizures.Psychoticbehavior,memorylossbecomeevidentlater.HSE-Clinicalfeature3.Neurologicsymptomandsignhemiparesis,aphasia,meningealrritatioin,disorderofconciousness,focalorgeneralizedseizures.Itmayresultincomaordeathinsomecases.HSE--LaboratoryDiagnosis1．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、海馬及邊沿系統(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)檢核對診療頗故意義①檢測HSV抗原②檢測HSV特異性lgM、lgG抗體③CSF中HSV-DNA（PCR快速診療）腦組織病理學(xué)及病原學(xué)檢查HSE--LaboratoryDiagnosisEEG:lateralizedhigh-voltageslow-waves.CTscansshowhypodensityoftheaffectedareas.MRIshowssignalchangesinalmostall.圖1圖2圖3CSF: increasedpressure,lymphocyticpleocytosis,mildproteinelevationandnormalglucose.HSE--LaboratoryDiagnosisTestsforthedetectionofHSVantigenintheCSFbytheapplicationofPCRareuseful.Theabsolutewayfordianosis:fluorecentantibodystudyandviralcultrueofcerebraltissueobtainedbybrainbiopsy.HSE--diagnosis1．臨床診療根據(jù)：①口唇或生殖道皰疹史；②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；③腦脊液紅、白細(xì)胞數(shù)增多，糖和氯化物正常；④腦電圖以顳、額區(qū)損害為主的腦彌漫性異常；⑤頭顱CT或MRI發(fā)現(xiàn)顳葉局灶性出血性腦軟化灶；⑥特異性抗病毒藥品治療有效。2.實(shí)驗(yàn)室檢查：CSF病原體檢查及病理檢查HSE—Differentialdiagnosis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早期體現(xiàn)，可有腦神經(jīng)損害，CSF檢查提示診療。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-treatmentAntiviralagentsTherewasnospecifictreatmentforHVEuntillthelate1970sacyclovirwasintroduced.Acyclovirandgancicloviraremosteffectivedrugs.Theysignificantlyreduceboththemortalityandmorbidity.HSE--treatment1．抗病毒化學(xué)藥品治療(1)無環(huán)鳥苷(阿昔洛韋,acyclovir)(2)更昔洛韋(ganciclovir)2．免疫治療①干擾素及其誘生劑②轉(zhuǎn)移因子③腎上腺皮質(zhì)激素3．全身支持治療4．對癥治療Creutzfeldt-JakobDisease

Creutzfeldt-Jakob病(CJD)是最常見的人類朊蛋白?。ň邆魅拘缘碾玫鞍姿碌纳l(fā)性中樞神經(jīng)系統(tǒng)變性疾?。?/p>

CJDisalsocalledSubacuteSpongiformEncephalopathy.(SSE)Itbelongs

tothecategorycalledthetransmissiblespongiformencephalopathies(priondiseases)PrPandprionProteindease朊蛋白(prionprotein,PrP)一種既含有傳染性又缺少核酸的非病毒性致病因子Prionisneitheravirusnoraviroid(nucleicacidalone,withoutacapsidstructure)buttheconversionofanormalcellularprotein.PrPandprionProteindease人類朊蛋白病尚有Kuru病、Gerstmann-Straussler綜合征(GSS)、致死性家族性失眠癥(FFI)、缺少特性性病理變化的朊蛋白癡呆和伴痙攣性截癱的朊蛋白癡呆。WhatisCJD?Refertoadistinctivecerebraldiseaseinwhicharapidlyprogressiveandprofounddementiaassociatedwithcerebellarataxia,diffusemyoclonicjerksandavarietyofothervisualandneurologicabnormalities.TheoutstandingfeaturesoftheneuropathologicchangesarewidespreadneuronallossandgliosisaccompaniedbyastrikingvacuolationorspongystateoftheaffectedregionsCJD-PathogenesisandType1型和2型存在于散發(fā)性CJD(sporadiculaCJD)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足消毒的腦電極而傳輸 Type-3:iatrogenicCJDbytransplantationofcorneasandimplantationofinfecteddepthelectrdesetc.CJD-Pathogenesis4型是新變異型-與瘋牛病(MCD)含有相似的種系特異性PrP基因突變形成遺傳性家族型CJDCJD-Pathology大致--腦呈海綿狀變化，皮質(zhì)、基底節(jié)和脊髓萎縮變性。Spongyappearanceshowsincerebralandcerebellarcortex.

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。WidespreadneuronallossandgliosisaccompaniedbyastrikingvacuolationandPrPsc

intheaffectedregions.CJD-臨床體現(xiàn)1．發(fā)病年紀(jì)25~78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(jìn)行性發(fā)展①早期：體現(xiàn)頗似神經(jīng)癥，可有頭痛、眩暈、共濟(jì)失調(diào)及視覺障礙等②中期：進(jìn)行性癡呆為重要體現(xiàn)，伴人格變化，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，最具特性性③晚期：出現(xiàn)尿失禁、無動(dòng)性沉默、昏迷等3．變異型CJD臨床體現(xiàn)共濟(jì)失調(diào)和行為變化CJD-clinicalfeature1.Itoccursmostlyinthelatemiddleage,althoughcanoccurinyoungadult.2.Progressivedevelopment. Theearlystage:Atypical Themidstage:gradualdementiawithpersonalitychange.Myoclonusoccursin2/3ofpatients.

Thelatestage:Coma,akineticmutism.3.VariantCJDCJD-LaboratoryFinding1．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(jìn)展呈持續(xù)性增高）。2．腦電圖：疾病中晚期可出現(xiàn)間隔0.5~2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-LaboratoryFindingTestofCSFbyimmunoassay,thefindingof14-3-3proteinisveryusefulinseparatingSSE.AlsoistheserumP-100.EEG:Highvoltageslowandsharp-wavecomplexes(0.5-2Hz).MRIsubtlehyperintensityofthelenticularnucleionT2weightedimageswhenthediseaseisfullyestablished.CJD-Diagnosis(診療原則)很可能(probable)CJD①在2年內(nèi)發(fā)生的進(jìn)行性癡呆；②肌陣攣、視力障礙、小腦癥狀、無動(dòng)性沉默等四項(xiàng)中含有其中兩項(xiàng)；③腦電圖周期性同時(shí)放電的特性性變化。如病人腦活檢發(fā)現(xiàn)海綿狀態(tài)和PrPSC者，則為確診的CJD?？捎媚X蛋白檢測替代腦電圖特異性變化。CJD-DiagnosisProbableSSE 1)Progressivedementiain2years 2)Twoofmyoclonus,visualdisterbance,ataxiaandakineticmutism. 3)EEG:synchronousdischarge.DefinitediagnosisSpongyorPRPscisfoundbybraintissuebiopsy.CJD-鑒別診療Alzheimer病進(jìn)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能達(dá)成治療目的90%病例于病后1年內(nèi)死亡腦囊蟲病CerebralCysticercosis

CerebralCysticercosis由豬帶絳蟲蚴蟲(囊尾蚴)寄生腦組織形成包囊所致。Cysticercosisisthelarvalstage(cysticercus)ofinfectionwiththeporktapeworm.CerebralCysticercosis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。Cysticercosisisaleadingcauseofepilepsyandotherneurologicdisturbances.腦囊蟲病-病因及發(fā)病機(jī)制

最常見的傳輸途徑是攝入帶有蟲卵污染的食物少見因素為肛門-口腔轉(zhuǎn)移而形成的本身感染或者是絳蟲的節(jié)片逆行入胃蟲卵進(jìn)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5~10mm，可有薄壁包膜，或呈多個(gè)囊腔

Thecystsmaybe5-10mm.The lesionsaremostoftenmultiplebutmaybesolitary.Cysticercosis-Pathology腦實(shí)質(zhì)中包囊內(nèi)存活的蚴蟲極少引發(fā)炎癥，普通在感染后數(shù)年蚴蟲死亡后才出現(xiàn)明顯的炎癥反映 Onlywhenthecystdegeneratedmanymonthsoryearsaftertheinitialinfestation,aninflammatoryandgranulomatousreactioniselicitedandfocalsymptomsarise.腦囊蟲病-ClinicalFeature1．腦實(shí)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(dòng)的包囊，可忽然阻塞第四腦室正中孔，造成腦壓忽然增高，引發(fā)眩暈、嘔吐、意識障礙和跌倒）。4．脊髓型非常罕見ClinicalFeatureThecerebralmanifestationsofcysticercosisarediverse,relatedtotheencystmentandsubsequentcalcificationofthelarvaeincerebralparenchyma,subarachnoidspaceandventricle.TheflowofCSFmaybeobstructedbylargesubarachnoidorintraventricularcystandleadstoobstructivehydrocephalus.腦囊蟲病-LaboratoryDiagnosis1．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(gè)或多個(gè)鈣化點(diǎn)，C