中樞神經系統感染

INFECTIONSOFTHECENTRALNERVOUSSYSTEM

NeurologyDepartmentTheSecondHospitalofHarbinMedicalUniversity第一節概述

Term：InfectionsofCNS

Allkindsofpathogen(bacteia,viruses,spirochete,parasites,fungi,rickettsiaandprionprottein) invadecerebralparenchyma,meningesandbloodvesselleadtoacuteandsubacuteinfections.第一節概述分類：感染的部位；發病狀況及病程；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識第二節病毒感染性疾病

ViralinfectionsofCNS單純皰疹病毒性腦炎HerpesSimplexEncephalitis

Creutzfeldt-JakobDiseaseHerpesSimplexEncephalitis

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

HSE--CausesandMechanismsHSV-嗜神經(neurotropic)DNA病毒90%的人類HSE是由I型引發70%HSE起因于內源性病毒的活化(復發性皰疹感染)25%的病例是原發感染(口腔和呼吸道)6%~15%系由II型所致(產婦生殖道HSV-II原發感染)絕大多數新生兒的HSE系HSV-II引發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細胞增生 Intensehemorrhagicnecrosisoftheinferiorandmedialpartsofthetemporallobesandthemedial-orbitalpartsofthefrontallobes.HSE-PathologyCowdryA型包涵體(Atypeinclusionbody)存在于病灶邊沿的部分神經細胞核內及星型細胞和少突膠質細胞核內。

HSE--Clinicalfeature1．任何年紀、季節均可發病原發感染的潛伏期為2~21天，平均6天；前驅期癥狀2．病程多急性起病，口唇皰疹史（1/4），高熱，首發癥狀：頭痛、輕微的意識和人格變化或全身性或部分性運動性發作；病情緩慢進展精神癥狀體現突出智能障礙也較明顯3．神經癥狀局灶性腦損害；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-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，也可見一側或雙側顳葉、海馬及邊沿系統局灶性低密度區3．腦脊液檢查壓力及細胞數正常或輕度增高，重癥者可明顯增高。4．腦脊液病原學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）腦組織病理學及病原學檢查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：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系統損害體征；③腦脊液紅、白細胞數增多，糖和氯化物正常；④腦電圖以顳、額區損害為主的腦彌漫性異常；⑤頭顱CT或MRI發現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.實驗室檢查：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病結核性腦膜腦炎：結核病病史或接觸史，慢性過程，腦膜刺激征是TBM早期體現，可有腦神經損害，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，可為流行性或散發性帶狀皰疹病毒性腦炎HSE-treatmentAntiviralagentsTherewasnospecifictreatmentforHVEuntillthelate1970sacyclovirwasintroduced.Acyclovirandgancicloviraremosteffectivedrugs.Theysignificantlyreduceboththemortalityandmorbidity.HSE--treatment1．抗病毒化學藥品治療(1)無環鳥苷(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轉移因子③腎上腺皮質激素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病（具傳染性的朊蛋白所致的散發性中樞神經系統變性疾病）

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型存在于散發性CJD(sporadiculaCJD)3型為醫源性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、基底節和脊髓萎縮變性。Spongyappearanceshowsincerebralandcerebellarcortex.

CJD-Pathology顯微鏡下--神經元丟失、星形細胞增生、細胞胞漿中空泡形成，可發現感染組織內異常PrP淀粉樣斑塊。WidespreadneuronallossandgliosisaccompaniedbyastrikingvacuolationandPrPsc

intheaffectedregions.CJD-臨床體現1．發病年紀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，緩慢進行性發展①早期：體現頗似神經癥，可有頭痛、眩暈、共濟失調及視覺障礙等②中期：進行性癡呆為重要體現，伴人格變化，有失語、偏癱、錐體束征或肌肉萎縮及2/3病人出現肌陣攣，最具特性性③晚期：出現尿失禁、無動性沉默、昏迷等3．變異型CJD臨床體現共濟失調和行為變化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。血清S100蛋白（隨病情進展呈持續性增高）。2．腦電圖：疾病中晚期可出現間隔0.5~2秒周期性棘-慢復合波。3．晚期CT和MRI：可見腦萎縮；MRI顯示雙側尾狀核、殼核T2呈對稱性均質高信號，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年內發生的進行性癡呆；②肌陣攣、視力障礙、小腦癥狀、無動性沉默等四項中含有其中兩項；③腦電圖周期性同時放電的特性性變化。如病人腦活檢發現海綿狀態和PrPSC者，則為確診的CJD。可用腦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。應用反義寡核苷酸或基因治療可能達成治療目的90%病例于病后1年內死亡腦囊蟲病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-病因及發病機制

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-口腔轉移而形成的本身感染或者是絳蟲的節片逆行入胃蟲卵進入十二指腸內孵化逸出六鉤蚴，蚴蟲經血液循環分布全身并發育成囊尾蚴，有不少囊尾蚴寄生在腦內。腦囊蟲病-Pathology典型的包囊大小為5~10mm，可有薄壁包膜，或呈多個囊腔

Thecystsmaybe5-10mm.The lesionsaremostoftenmultiplebutmaybesolitary.Cysticercosis-Pathology腦實質中包囊內存活的蚴蟲極少引發炎癥，普通在感染后數年蚴蟲死亡后才出現明顯的炎癥反映 Onlywhenthecystdegeneratedmanymonthsoryearsaftertheinitialinfestation,aninflammatoryandgranulomatousreactioniselicitedandfocalsymptomsarise.腦囊蟲病-ClinicalFeature1．腦實質型臨床癥狀與包囊的位置有關。2．蛛網膜型頭痛、腦積水和虛性腦膜炎等。3．腦室型阻塞性腦積水；布龍(Brun)征發作（移動的包囊，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．血常規檢查嗜酸性粒細胞增多。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可發現腦積水及被阻塞的部位，CT可見單個或多個鈣化點，C