神經病學課件：中樞神經系統感染

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1、Infections of Central Nervous SystemInfections of Central Nervous SystemAll kinds of All kinds of pathogenpathogeninvadeinvadecerebral parenchymacerebral parenchymameninges meninges and blood vesseland blood vessellead to lead to acute acute subacutesubacuteor chronicor chronicinfections.infections.

2、BacteriaBacteriaVirusesVirusesParasitesParasitesFungiFungiPrion proteinPrion proteinSpirocheteSpirocheteRickettsia Rickettsia-Classification according-Classification according to the pathogento the pathogenPurulent MeningitisPurulent MeningitisTuberculous MeningitisTuberculous MeningitisHerpes Simpl

3、ex Virus EncephalitisHerpes Simplex Virus EncephalitisCerebral CysticercosisCerebral CysticercosisCryptococcal MeningitisCryptococcal MeningitisCreutzfeldt-Jakob diseaseCreutzfeldt-Jakob diseaseCentral Nervous System Syphilis-Classification according-Classification according to the pathologyto the p

4、athologynParenchyma Parenchyma encephalitis encephalitis myelitis myelitis encephalomyelitis encephalomyelitis nMeninges Meninges meningitis meningitis nParenchyma&Meninges Parenchyma&Meninges meningoencephalitis meningoencephalitisPathway of Pathway of infectioninfectionHematogenous spreadHematogen

5、ous spreadDirect infectionDirect infectionPeripheral nerves pathwayPeripheral nerves pathwayneurotropic virus,HSVneurotropic virus,HSVViral Viral infections of CNSinfections of CNS無菌性腦無菌性腦膜炎膜炎腦炎腦炎麻痹性麻痹性疾病疾病合計合計腮腺炎腮腺炎282811111 14040淋巴細胞性脈絡淋巴細胞性脈絡叢腦膜炎病毒叢腦膜炎病毒7 70 00 07 7單純皰疹病毒單純皰疹病毒2 27 70 09 9脊髓灰質炎病毒

6、脊髓灰質炎病毒18185 566668989科薩基病毒科薩基病毒A A18181 10 01919科薩基病毒科薩基病毒B B71714 40 07575?？刹《景？刹《?5553 31 15959蟲媒病毒蟲媒病毒3 35 50 08 8nEncephalitis can develop following a wide range of viral Encephalitis can develop following a wide range of viral infection.This results in different clinical manifestations,infecti

7、on.This results in different clinical manifestations,different levels of severity,and potential for long-term different levels of severity,and potential for long-term neurologic neurologic sequelaesequelae.nMany non-viral disorders of CNS enter into the Many non-viral disorders of CNS enter into the

8、 differential diagnosis of suspected viral encephalitis and differential diagnosis of suspected viral encephalitis and further complicate diagnostic efforts.further complicate diagnostic efforts.nParamount importance is the rapid identification of Paramount importance is the rapid identification of

9、herpes simplex encephalitis herpes simplex encephalitis because the prompt because the prompt initiation of acyclovir is indicated.initiation of acyclovir is indicated.nOtherwise,specific antiviral chemotherapy is presently Otherwise,specific antiviral chemotherapy is presently unavailable for viral

10、 encephalitis not caused by HSV.unavailable for viral encephalitis not caused by HSV.nIn these cases,adequacy of supportive care and In these cases,adequacy of supportive care and prompt management of specific neurologic prompt management of specific neurologic complications help improve patients pl

11、ications help improve patients outcome.Herpes Simplex EncephalitisHerpes Simplex Encephalitisn單純皰疹病毒所引起的急性中樞神經系統感染單純皰疹病毒所引起的急性中樞神經系統感染 急性出血壞死性腦炎急性出血壞死性腦炎 急性包涵體性腦炎急性包涵體性腦炎 n單純皰疹病毒單純皰疹病毒 DNA DNA病毒病毒 I I 型單純皰疹病毒型單純皰疹病毒 成人：感染后病毒潛伏于三叉神經半月節，成人：感染后病毒潛伏于三叉神經半月節，抵抗力低下時發病抵抗力低下時發病 少數兒童及青年：原發性感染，通過嗅神經少數兒童及青年：原發

12、性感染，通過嗅神經 軸突直接侵犯腦組織軸突直接侵犯腦組織 II II型單純皰疹病毒型單純皰疹病毒 主要感染性器官，子宮內感染、產道內感染、主要感染性器官，子宮內感染、產道內感染、經血行傳播而致經血行傳播而致新生兒腦炎新生兒腦炎。Herpes virusesHerpes virusesn大體大體雙側大腦半球彌漫性侵犯，常不對稱。雙側大腦半球彌漫性侵犯，常不對稱。以海馬回、顳中回、額葉眶面和扣帶回等處受累以海馬回、顳中回、額葉眶面和扣帶回等處受累最明顯最明顯n表現表現腦實質局部壞死、軟化、出血、水腫，腦實質局部壞死、軟化、出血、水腫，嚴重可導致顳葉鉤回疝。嚴重可導致顳葉鉤回疝。n鏡下鏡下神經細胞變

13、性、脫落，可見噬節和衛神經細胞變性、脫落，可見噬節和衛星現象，核內有星現象，核內有嗜酸性嗜酸性CowdryCowdry A A型包涵體型包涵體n病變腦組織及腦膜有充血、滲出，病變腦組織及腦膜有充血、滲出，血管周圍可血管周圍可見淋巴細胞和漿細胞浸潤見淋巴細胞和漿細胞浸潤n急性期后神經膠質細胞增生腦組織萎縮急性期后神經膠質細胞增生腦組織萎縮 病理特征病理特征-腦實質出血壞死和細胞內包涵體腦實質出血壞死和細胞內包涵體n任何年齡均可發病任何年齡均可發病n急性起病，也可亞急性起病急性起病，也可亞急性起病n前驅癥狀前驅癥狀發熱、全身不適、頭痛等發熱、全身不適、頭痛等n1/41/4患者有口唇皰疹史患者有口唇

14、皰疹史n腦實質損害的臨床表現腦實質損害的臨床表現 意識障礙意識障礙 精神癥狀精神癥狀 癲癇發作癲癇發作 局灶定位體征局灶定位體征腦電圖腦電圖彌漫性高波幅慢彌漫性高波幅慢波，顳區的尖波與棘波波，顳區的尖波與棘波頭頭CTCT可正常，也可可正常，也可見海馬及邊緣系統局灶見海馬及邊緣系統局灶性低密度，及出血壞死。性低密度，及出血壞死。MRIMRI有助于發現病灶有助于發現病灶A:T2-weighted axial MRI reveals high signal intensity in the right insular cortex,medial right frontal cortex(solid

15、arrow),and left insular cortex(open arrow).B:T2-weighted coronal MRI shows increased signal in the left temporal lobe and early involvement of the right side.An abnormal MR image is usually seen by day 1 or 2 after the onset of manifestations.Coronal images are the most useful for detecting the herp

16、es simplex lesions.nCSFCSF壓力正?；蛟龈?，細胞數增多，蛋白輕、壓力正?；蛟龈?，細胞數增多，蛋白輕、中度增高，糖和氯化物正常中度增高，糖和氯化物正常nCSFCSF病原學檢查病原學檢查HSVHSV抗原、特異性抗原、特異性IgMIgM、IgGIgG抗體；抗體；HSV-DNAHSV-DNA有確診價值有確診價值n確診有賴于腦組織活檢確診有賴于腦組織活檢可見出血壞死，可見出血壞死，電鏡下見電鏡下見CowdryCowdry A A包涵體；也可作病毒分離包涵體；也可作病毒分離1.1.口唇或生殖道皰疹史?？诖交蛏车腊捳钍?。2.2.發熱、精神癥狀、意識障礙、抽搐及局灶性神經體征。發熱、

17、精神癥狀、意識障礙、抽搐及局灶性神經體征。3.3.CSFCSF示紅白細胞數增多或正常。示紅白細胞數增多或正常。4.4.腦電圖示以額顳為主的彌漫性異常。腦電圖示以額顳為主的彌漫性異常。5.5.頭頭CTCT或或MRIMRI示額顳葉出血壞死性病灶。示額顳葉出血壞死性病灶。6.6.CSFCSF發現發現HSVHSV抗原或抗體?？乖蚩贵w。7.7.CSF PCRCSF PCR檢測發現該病毒檢測發現該病毒DNADNA。8.8.腦組織或腦脊液標本腦組織或腦脊液標本HSVHSV分離、培養或鑒定。分離、培養或鑒定。9.9.腦活檢：組織細胞核內發現包涵體，或原位雜交發現腦活檢：組織細胞核內發現包涵體，或原位雜交發現

18、HSVHSV病毒核酸病毒核酸10.10.特異性抗單純皰疹病毒治療有效。特異性抗單純皰疹病毒治療有效。n 帶狀皰疹病毒性腦炎：胸腰部帶狀皰疹史；為帶狀皰疹病毒性腦炎：胸腰部帶狀皰疹史；為免疫介導性腦損害，病變輕、預后好；病原學檢免疫介導性腦損害，病變輕、預后好；病原學檢查可確診。查可確診。n腸道病毒性腦炎：多見于夏秋季，病初可有腸道腸道病毒性腦炎：多見于夏秋季，病初可有腸道感染，感染，CSFCSF病毒分離或病毒分離或PCRPCR檢查陽性。檢查陽性。n巨細胞病毒性腦炎：見于免疫缺陷或巨細胞病毒性腦炎：見于免疫缺陷或AIDSAIDS或長或長期用免疫抑制劑治療者。期用免疫抑制劑治療者。n急性播散性腦脊

19、髓炎：感染后或疫苗接種后，免急性播散性腦脊髓炎：感染后或疫苗接種后，免疫介導性腦損害。疫介導性腦損害。n腦血管疾?。耗X葉的梗塞或出血，有發病的危險腦血管疾?。耗X葉的梗塞或出血，有發病的危險因素，無發熱感染的前驅癥狀。因素，無發熱感染的前驅癥狀。n功能性精神?。憾酂o神經系統定位體征，無意識功能性精神?。憾酂o神經系統定位體征，無意識障礙及發熱抽搐。障礙及發熱抽搐。n代謝性或中毒性腦?。焊涡阅X病、藥物中毒、酒代謝性或中毒性腦?。焊涡阅X病、藥物中毒、酒精中毒、精中毒、COCO中毒。中毒。n腦腫瘤：多為慢性或進行性發展，可有神經系統腦腫瘤：多為慢性或進行性發展，可有神經系統癥狀和體征。癥狀和體征。Sus

20、pect viral encephalitisFocal neurologic deficits presentEnhanced MRI&EEGNonfocalOther diagnosisFocal lesionLP safeLP not safeCSF HSV PCR+IV Acyclovir 10 mg/Kg q8h for 14 daysRepeat MRI Mononuclear pleocytosisAcellular or PMN pleocytosisOther diagnosisAppropriate managementFocal signs+Repeat from beg

21、inningAbsent Nonherpetic encephalitisSupportive care Repeat from beginning if patients deterioratesCSF HSV PCR+Temporal lobe lesionAcellular or PMN pleocytosisMononuclear pleocytosisWait 12-36hRepeat LPCSF HSV PCRBrain biopsy Begin IV acyclovir 10mg/Kg q8hHSV isolated nonStopAcute ManagementAcute Ma

22、nagement1.1.Center aroundCenter around the level of alertnessthe level of alertness airway protective reflexesairway protective reflexes respiratory drive respiratory drive 顱內壓增高顱內壓增高原發性腦干損傷原發性腦干損傷持續癎性發作或持續癎性發作或發作后嗜睡發作后嗜睡Treatment:Treatment:Intubation with mechanical ventilation Intubation with mech

23、anical ventilation2.2.Elevated Elevated ICP ICP？neurologic examinationneurologic examination brain imagingbrain imaging direct CSF pressure measurementdirect CSF pressure measurementTreatmentTreatment：理想的血漿滲透壓理想的血漿滲透壓 305305315mOsm315mOsm The head should be raised 30 degreesThe head should be raised

24、 30 degrees Fluid administration should be restrictedFluid administration should be restricted (1000-1500ml/day)(1000-1500ml/day)Osmotic agents MannitolOsmotic agents Mannitol SteroidsDexamethaseone(0.15mg/kg iv stSteroidsDexamethaseone(0.15mg/kg iv st 0.25mg/kg/day divided doses every 6 hours)0.25m

25、g/kg/day divided doses every 6 hours)Acute ManagementAcute Management3.3.SeizureSeizure Seizure may complicate acute viral encephalitis.Seizure may complicate acute viral encephalitis.Treatment:Treatment:anticonvulsantsanticonvulsants Prophylactic anticonvulsant therapy Prophylactic anticonvulsant t

26、herapy (unnecessary,unless brain biopsy)(unnecessary,unless brain biopsy)Following an isolated seizure Phenytoin Following an isolated seizure Phenytoin Status epilepticus DiazepamStatus epilepticus Diazepam iv iv oror FosphenytoinFosphenytoin iv;Phenytoin iv;Phenytoin popo 血藥濃度血藥濃度151525ug/ml25ug/m

27、l Duration of anticonvulsant therapyDuration of anticonvulsant therapy several months following recovery several months following recoveryAcute ManagementAcute Management4.4.Antiviral chemotherapyAntiviral chemotherapy A potential diagnosis of HSE begin intravenous A potential diagnosis of HSE begin

28、 intravenous acyclovir without delay acyclovir without delay (history,examination,neuroimaging,CSF profile (history,examination,neuroimaging,CSF profile）Outcome measure in HSEOutcome measure in HSE 癥狀出現至阿昔洛韋治療的時間癥狀出現至阿昔洛韋治療的時間 患者年齡患者年齡 就診時患者的意識障礙嚴重程度就診時患者的意識障礙嚴重程度TreatmentTreatment：intravenous acycl

29、ovir or ganciclovirintravenous acyclovir or ganciclovir Dosage Dosage：10mg/kg q8h10mg/kg q8h14-21days14-21days GFR 10-50ml/min2.5mg/kg q12hGFR 10-50ml/min2.5mg/kg q12h 10ml/min 2.5mg/kg q24h 10ml/min 2.5mg/kg q24hAcute ManagementAcute ManagementContinued ManagementContinued Management1.1.Maintain a

30、positive nitrogen balanceMaintain a positive nitrogen balance2.2.Serum electrolytic balanceSerum electrolytic balance3.3.Paradoxical antidiuretic hormone secretionParadoxical antidiuretic hormone secretion4.4.Renal dysfunctionRenal dysfunction5.5.Prophylaxis against deep venous thrombosisProphylaxis

31、 against deep venous thrombosis6.6.Prophylaxis against gastrointestinal ulcerationProphylaxis against gastrointestinal ulceration7.7.Rehabilitating train Rehabilitating train Herpes ZosternHerpes zoster is characterized by pain and rash,usually restricted to two or three dermatomes.nIt was caused by

32、 reactivation of varicella-zoster virus latent in cranial or dorsal ganglia since childhood chickenpox.Herpes Zoster50y 1.Analgesia 2.Antivirals not required but may speed healing of rashImmunocompetent Immunocompromised Acyclovir iv 5-10mg/kg q8h 5-7 days50y1.Famciclovir 500mg tid 2.Analgesia3.Pred

33、nisone 60mg po 3-5 daysHerpes ZosterTreatment of Post-herpetic Neuralgia 1.Topical agents:水楊酸三乙醇胺乳膏劑水楊酸三乙醇胺乳膏劑2.Amitriptyline 25-75mg/d 3.Carbamazepine 600-1200mg/d 4.Gabapentin 900-3600mg/d 5.Oxycodone 10-30mg/d 羥氫可待酮羥氫可待酮6.Diazepam 2mg tid謝謝 謝謝!病毒性腦膜炎病毒性腦膜炎Viral Meningitis概念概念n是一組由各種病毒感染引起的軟腦膜是一組由

34、各種病毒感染引起的軟腦膜彌漫性炎癥的臨床綜合征彌漫性炎癥的臨床綜合征病因及發病機制病因及發病機制n85%85%95%95%由腸道病毒引起由腸道病毒引起n消化道感染消化道感染病毒與腸道細胞結合病毒與腸道細胞結合入血入血病毒血癥病毒血癥中樞神經系統中樞神經系統病理病理n側腦室和第四腦室的脈絡叢炎癥細胞浸潤。側腦室和第四腦室的脈絡叢炎癥細胞浸潤。n室管膜內層局灶性破壞的血管壁纖維化以室管膜內層局灶性破壞的血管壁纖維化以及纖維化的基底軟腦膜炎。及纖維化的基底軟腦膜炎。n室管膜下的星形細胞增多和增大。室管膜下的星形細胞增多和增大。臨床表現及輔助檢查臨床表現及輔助檢查n夏秋季高發，熱帶和亞熱帶發病率高。夏

35、秋季高發，熱帶和亞熱帶發病率高。85%-95%85%-95%由腸道病毒引起，該病毒屬于微小核糖核酸病毒由腸道病毒引起，該病毒屬于微小核糖核酸病毒科，有科，有6060多個亞型，包括脊髓灰質炎病毒、柯薩多個亞型，包括脊髓灰質炎病毒、柯薩奇病毒奇病毒A A和和B B、?？刹《镜?。、?？刹《镜?。n兒童多見，成人也可發病。兒童多見，成人也可發病。n急性發病，病程常持續急性發病，病程常持續1-21-2周。周。n臨床表現：臨床表現：全身中毒癥狀：如發熱、畏光、肌痛、食欲全身中毒癥狀：如發熱、畏光、肌痛、食欲 減退、腹瀉和全身乏力等減退、腹瀉和全身乏力等 腦膜刺激征：頭痛、嘔吐、頸強和腦膜刺激征：頭痛、嘔吐、

36、頸強和KernigKernig征等征等nCSFCSF壓力可能增高，細胞數增多壓力可能增高，細胞數增多10-100010-100010106 6/L/L，早期以多形核為主，早期以多形核為主，8-48h8-48h后以淋巴細胞為主。后以淋巴細胞為主。蛋白可輕度增高，糖、氯水平正常蛋白可輕度增高，糖、氯水平正常nPCRPCR檢查病毒陽性。檢查病毒陽性。臨床表現及輔助檢查臨床表現及輔助檢查診斷及治療診斷及治療n確診確診需腦脊液病毒學檢查需腦脊液病毒學檢查n治療治療是自限性疾病，抗病毒治療可以是自限性疾病，抗病毒治療可以縮短病程，主要是對癥支持治療（止痛、縮短病程，主要是對癥支持治療（止痛、抗癲癇、脫水治

37、療等）?？拱d癇、脫水治療等）。朊蛋白病朊蛋白病Prion Disease概述概述n由具傳染性的由具傳染性的朊蛋白朊蛋白（Prion protein,PrP）所致的一組中樞神經系統變性疾病所致的一組中樞神經系統變性疾病n動物朊蛋白病動物朊蛋白病 羊瘙癢病、傳染性水貂腦病、羊瘙癢病、傳染性水貂腦病、麋鹿和騾鹿慢性消耗病、牛海綿狀腦病麋鹿和騾鹿慢性消耗病、牛海綿狀腦病n人類朊蛋白病人類朊蛋白病 CJDCJD、KuruKuru病、病、Gerstmann-Gerstmann-StrausslerStraussler SynSyn(GSS)(GSS)、fatal familial fatal famili

38、al insomnia(FFI insomnia(FFI 致命性家族性失眠癥致命性家族性失眠癥)、朊蛋白、朊蛋白癡呆癡呆n朊蛋白朊蛋白(Prion protein,PrP)-(Prion protein,PrP)-既具有傳既具有傳染性又缺乏核酸的非病毒性致病因子染性又缺乏核酸的非病毒性致病因子 概述概述概述概述Creutzfeldt-Jakob Creutzfeldt-Jakob 病病n最常見的人類朊蛋白病，主要累及皮質、基最常見的人類朊蛋白病，主要累及皮質、基底節和脊髓，故又稱為皮質紋狀體脊髓底節和脊髓，故又稱為皮質紋狀體脊髓變性。變性。n多見于老年人。多見于老年人。nPrPPrP可通過角膜

39、、硬腦膜移植、經腸道外給予可通過角膜、硬腦膜移植、經腸道外給予人生長激素制劑和埋藏未充分消毒的腦電極人生長激素制劑和埋藏未充分消毒的腦電極而傳播而傳播分型分型n1 1型和型和2 2型存在于散發性型存在于散發性CJDCJD。n3 3型型Type-3Type-3為醫源性為醫源性(iatrogenic)(iatrogenic)。n4 4型是新變異型型是新變異型-與瘋牛病與瘋牛病(MCD)(MCD)具有相似的具有相似的種系特異性。種系特異性。nPrPPrP基因突變形成遺傳性家族型基因突變形成遺傳性家族型CJDCJD。Creutzfeldt-Jakob Creutzfeldt-Jakob 病病Gross

40、 evident:cerebral atrophyMicroscopic findings:neuronal loss,astrocytosis,and the development of cytoplasmic vacuoles in neurons and astrocytes(status spongiosis);Amyloid plaques containing the abnormal PrP;no inflammationThe cortex and basal ganglia are most affected,but all parts of the neuraxis ma

41、y be involved.病理改變病理改變CJDCJD臨床表現臨床表現n隱襲起病，緩慢進行性發展。隱襲起病，緩慢進行性發展。n分三期分三期初期：初期：神經癥表現，頭痛、眩暈、共濟失調神經癥表現，頭痛、眩暈、共濟失調中期：中期：進行性癡呆、脊髓前角損害出現肌萎縮、進行性癡呆、脊髓前角損害出現肌萎縮、肌陣肌陣 攣（最具特征性）攣（最具特征性）、錐體束征。、錐體束征。晚期：晚期：尿失禁、無動性緘默、昏迷與去皮層強直尿失禁、無動性緘默、昏迷與去皮層強直 狀態，可因褥瘡或肺感染而死亡狀態，可因褥瘡或肺感染而死亡CJDCJD輔助檢查輔助檢查n熒光免疫檢測熒光免疫檢測CSFCSF中中14143 33 3蛋

42、白蛋白可呈陽性?？沙赎栃?。n血清血清S S100100蛋白蛋白隨病情進展而持續性增高。隨病情進展而持續性增高。n腦電圖可出現腦電圖可出現棘慢復合波棘慢復合波。n晚期晚期CTCT或或MRIMRI出現腦萎縮；出現腦萎縮；MRIMRI示雙側尾狀核、示雙側尾狀核、殼核殼核T2T2對稱性均質高信號，很少波及蒼白球，對稱性均質高信號，很少波及蒼白球，T1T1正常，對診斷有意義。正常，對診斷有意義。Record of a 65-year-old man shows spikes of sharp waves at intervals of 0.7 seconds throughout the recordi

43、ng.Such periodicity with 0.5-to 2.0-second intervals occurs in the middle and late stages and may be absent in the early stages of the disease.診斷診斷n在在2 2年內發生的進行性癡呆。年內發生的進行性癡呆。n肌陣攣、視力障礙、小腦癥狀、無動性緘默肌陣攣、視力障礙、小腦癥狀、無動性緘默4 4項中具項中具2 2項。項。n腦電圖特征性改變。腦電圖特征性改變。診斷：診斷：具備具備3 3項為很可能項為很可能CJDCJD，僅具，僅具1 1、2 2項為項為可能可能C

44、JDCJD，確診需靠腦活檢，確診需靠腦活檢nAlzheimerAlzheimer病病n進行性核上性麻痹進行性核上性麻痹n橄欖腦橋小腦萎縮橄欖腦橋小腦萎縮n腦囊蟲病腦囊蟲病n肌陣攣性癲等鑒別肌陣攣性癲等鑒別鑒別診斷鑒別診斷Tuberculous meningitisTBMOverviewnTBM differs from that caused by most TBM differs from that caused by most other common bacteria in that other common bacteria in that the course is more pro

45、longedthe course is more prolonged the mortality rate is higherthe mortality rate is higher CSF changes are less severeCSF changes are less severe treatment is less effective intreatment is less effective in preventing sequelae preventing sequelae PathogenesisnTBM is always secondary to TB elsewhere

46、 TBM is always secondary to TB elsewhere in the bodyin the bodynThe primary focus is usually in the The primary focus is usually in the lungs but may be in the lymph glands,lungs but may be in the lymph glands,bones,nasal sinuses,gastrointestinal bones,nasal sinuses,gastrointestinal tract,or any org

47、an in the body.tract,or any organ in the body.nThe onset of meningeal symptoms may The onset of meningeal symptoms may coincide with signs of acute miliary coincide with signs of acute miliary dissemination,or there may be dissemination,or there may be clinical evidence of activity in the clinical e

48、vidence of activity in the primary focus;primary focus;however,meningitis is however,meningitis is often the only manifestation of the often the only manifestation of the disease.disease.n結核菌經血播散結核菌經血播散腦膜、軟腦膜下種植腦膜、軟腦膜下種植結結核結節核結節結節破潰結節破潰蛛網膜下腔蛛網膜下腔PathogenesisPotts disease(spinal tuberculosis).A:T2W s

49、agittal magnetic resonance(MR)scan:increased signal intensity within four to five consecutive vertebral bodies of the lower thoracic spine,compression fracture of one of the thoracic vertebral bodies.B and C:T1W sagittal MR scans of thoracic spine before and after gadolinium enhancement show marked

50、enhancement of affected thoracic vertebral bodies with mild epidural extension,especially at the level of the compression fracture.Pathology1.1.The meningesThe meningescloudy and thickened cloudy and thickened most intense at the base of the brain.most intense at the base of the brain.2.2.A thick co

51、llar of fibrosisA thick collar of fibrosisaround the around the optic nerves,cerebral peduncles,the optic nerves,cerebral peduncles,the pons and midbrain.pons and midbrain.3.3.The ventriclesThe ventriclesmoderately dilated moderately dilated The ependymal liningThe ependymal liningcovered with cover

52、ed with exudate or appears roughened exudate or appears roughened(granular(granular ependymitis ependymitis 顆粒性室管膜炎顆粒性室管膜炎)4.4.Minute tuberclesMinute tuberclesbe visible in the be visible in the meninges,choroid plexus,and cerebral meninges,choroid plexus,and cerebral parenchyma.parenchyma.Pathology

53、microscopy1.1.The exudateThe exudatemononuclear cells,mononuclear cells,lymphocytes,plasma cells,macrophages,lymphocytes,plasma cells,macrophages,and fibroblasts with an occasional giant and fibroblasts with an occasional giant cell.cell.2.2.The inflammatory process may extend for a The inflammatory

54、 process may extend for a short distance into the cerebral substance short distance into the cerebral substance where microscopic granulomas may also be where microscopic granulomas may also be found.found.3.3.Proliferative changes are frequently seen Proliferative changes are frequently seen in the

55、 inflamed vessels of the meninges,in the inflamed vessels of the meninges,producing a pan-arteritisproducing a pan-arteritislead to lead to thrombosis of the vessel and cerebral thrombosis of the vessel and cerebral infarcts.infarcts.EpidemiologyIncidencen活動性結核活動性結核 8 8百百萬年萬年nTBMTBM7 7萬年萬年 CNSCNS結核瘤

56、和腦實質肉結核瘤和腦實質肉芽腫芽腫10102020high risk populationn艾滋病患者艾滋病患者n結核病密切接觸者結核病密切接觸者n酒精中毒或營養不良者酒精中毒或營養不良者n流浪者流浪者n老年人老年人n長期使用類固醇或免疫長期使用類固醇或免疫抑制劑者抑制劑者n偏遠落后地區偏遠落后地區n其他部位結核病者其他部位結核病者Clinical Manifestationn亞急性或急性起病，慢性過程。亞急性或急性起病，慢性過程。n結核中毒癥狀、腦膜刺激征。結核中毒癥狀、腦膜刺激征。n腦積水，顱高壓（交通性或梗阻性腦積水）。腦積水，顱高壓（交通性或梗阻性腦積水）。n治療不及時可出現腦實質損害

57、癥狀。治療不及時可出現腦實質損害癥狀。n顱神經損害，脊髓損害。顱神經損害，脊髓損害。n老年患者顱高壓不明顯，老年患者顱高壓不明顯，CSFCSF改變不典型，常改變不典型，常發生結核性動脈內膜炎發生結核性動脈內膜炎 Auxiliary ExaminationnCSFCSF壓力增高，外觀黃色，靜止后可有薄膜形壓力增高，外觀黃色，靜止后可有薄膜形成，細胞數增多，淋巴細胞為主，蛋白升高，成，細胞數增多，淋巴細胞為主，蛋白升高，糖及氯化物降低糖及氯化物降低n抗酸桿菌染色，陽性低抗酸桿菌染色，陽性低n結核桿菌培養是確診的金指標，但陽性率低結核桿菌培養是確診的金指標，但陽性率低nMRIMRI和和CTCT檢查（

58、腦膜強化，猶以顱底腦膜明顯）檢查（腦膜強化，猶以顱底腦膜明顯）CSF change of TBM1.1.increased pressureincreased pressure2.2.slightly cloudy or ground-glass appearanceslightly cloudy or ground-glass appearance3.3.formation of a clot on standingformation of a clot on standing4.4.moderate pleocytosis of 25 to 500 cells/mmmoderate ple

59、ocytosis of 25 to 500 cells/mm3 3 lymphocytes as the predominating cell type lymphocytes as the predominating cell type5.5.increased protein contentincreased protein content6.6.decreased sugar content with values in the decreased sugar content with values in the range of 20 to 40 mg/dLrange of 20 to

60、 40 mg/dL7.7.a negative serologic test for syphilis or a negative serologic test for syphilis or cryptococcal antigencryptococcal antigenCSF change of TBM Although none of these abnormalities is Although none of these abnormalities is diagnostic,their occurrence in diagnostic,their occurrence in com

61、bination is usually pathognomonic and combination is usually pathognomonic and is sufficient evidence to warrant is sufficient evidence to warrant intensive therapy until the diagnosis can intensive therapy until the diagnosis can be confirmed by stained smears of the be confirmed by stained smears

62、of the sediment or pellicle or by culture of the sediment or pellicle or by culture of the CSF.CSF.A and B:(A)large nonenhancing hypodense lesion in the left temporal lobe and(B)left basal ganglia Significant basal cisternal enhancement consistent with meningitisC and D:T1W axial MRI after gadoliniu

63、m enhancement show florid contrast enhancement within basal cisterns most consistent with exudative meningitis of tuberculosis.Enhancement of the left temporal lobe and left basal ganglia lesions suggests persistent inflammation within these infarcts.Intracranial Multifocal Lesions Associated with P

64、hthisis Miliaris:Tuberculoma or Inflammatory Granuloma?DiagnosisnDiagnosis of TBM presents a challenge The mycobacterium is difficult to culture from CSF(positive rate 50%)Acid-fast staining(positive rate 5%-10%)Because isolation of mycobacterium requires several weeks,a rapid method of diagnosis is

65、 needed(TB DNA fragment PCR)Methods to improve the positive rateCulture of large volumes of CSF(10-30ml)3 30%75%High-speed centrifugation of the CSF for a prolonged period(3000gravity for 30 minutes)診斷及鑒別診斷診斷及鑒別診斷n診斷：診斷：結核病史及接觸史結核病史及接觸史 腦膜刺激征腦膜刺激征 腦脊液特征性改變腦脊液特征性改變 神經影像學特征性改變神經影像學特征性改變n鑒別：鑒別：其它腦膜炎如隱球

66、菌性腦膜炎其它腦膜炎如隱球菌性腦膜炎 蛛網膜下腔出血蛛網膜下腔出血 血管性頭痛血管性頭痛Management of TBM General priciple1.1.Multiple antimicrobial drugs are requiredMultiple antimicrobial drugs are required2.2.Drugs must adequately cross the blood-CSF Drugs must adequately cross the blood-CSF barrier to achieve therapeutic concentration in barrier to achieve therapeutic concentration in CSFCSF3.3.Drugs should be taken on a regular basisDrugs should be taken on a regular basis4.4.Drugs should be taken for a sufficient period Drugs should