INFECTIONS+OF+THE+CENTRAL+NERVOUS+SYSTEM+

中枢神经系统感染中枢神经系统感染 INFECTIONS OF THE CENTRAL NERVOUS SYSTEM Neurology DepartmentThe Second Hospital of Harbin Medical University第一节第一节 概述概述 nTerm：Infections of CNS All kinds of pathogen (bacteia,viruses,spirochete,parasites,fungi,rickettsia and prion prottein)invade cerebral parenchyma,meninges and blood vessel lead to acute and subacute infections.第一节第一节 概述概述n分类分类：感染的部位感染的部位；发病情况及病程；发病情况及病程；特异性致病因子；特异性致病因子 nCNS感染途径感染途径(pathway of infection)nhematogenous spread；ndirect infection；nPeripheral nerves pathwaynCNS病毒感染性疾病新的认识病毒感染性疾病新的认识 第二节第二节 病毒感染性疾病病毒感染性疾病 Viral infections of CNSn单纯疱疹病毒性脑炎单纯疱疹病毒性脑炎Herpes Simplex Encephalitis nCreutzfeldt-Jakob DiseaseHerpes Simplex Encephalitis n病因及发病机制病因及发病机制(Causes and Mechanisms)n病理（病理（pathology)n临床表现临床表现(Clinical features)n辅助检查辅助检查(laboratory finding)n诊断及鉴别诊断诊断及鉴别诊断(Diagnosis and Differential Diagnosis)n治疗（治疗（treatment)HSE-Causes and MechanismsnHSV-嗜神经嗜神经(neurotropic)DNA病毒病毒 n90%的人类的人类HSE是由是由I型型引起引起 n70%HSE起因于内源性病毒的活化起因于内源性病毒的活化(复发性疱疹感染复发性疱疹感染)n25%的病例是原发感染的病例是原发感染(口腔和呼吸道口腔和呼吸道)n6%15%系由系由II型型所致所致(产妇产妇生殖道生殖道HSV-II原发感染原发感染)n绝大多数新生儿的绝大多数新生儿的HSE系系HSV-II引起引起 HSE-Pathologyn颞颞叶、叶、额额叶等部位叶等部位出血性坏死出血性坏死|、渗渗出出n急性期后可见小胶质细胞增生急性期后可见小胶质细胞增生 Intense hemorrhagic necrosis of the inferior and medial parts of the temporal lobes and the medial-orbital parts of the frontal lobes.HSE-PathologynCowdry A型包涵体型包涵体(A type inclusion body)存在于病灶边缘的部存在于病灶边缘的部分神经细胞核内分神经细胞核内 及星型细胞和少突及星型细胞和少突胶质细胞核内。胶质细胞核内。HSE-Clinical featuren1任何任何年龄、季节年龄、季节均可发病原发感染的潜伏均可发病原发感染的潜伏期为期为221天，平均天，平均6天；前驱期症状天；前驱期症状n2病程病程 多急性起病多急性起病，口唇疱疹史口唇疱疹史（1/4），），高热高热，首发症状首发症状：头痛、轻微的意识和人格：头痛、轻微的意识和人格改变改变 或全身性或部分性运动性发作或全身性或部分性运动性发作；病情缓；病情缓慢进展慢进展精神症状精神症状表现突出智能障碍也较明显表现突出智能障碍也较明显 n3 神经症状神经症状 局灶性脑损害局灶性脑损害；脑膜刺激征；脑膜刺激征；意识障碍意识障碍；全身性或部分性；全身性或部分性癫痫癫痫。重症脑疝。重症脑疝形成而死亡形成而死亡（死亡率高达（死亡率高达40%70%）。）。HSE-Clinical featuren1.It occurs sporadically throughout the year and in patients of all ages.During prodromal stage:fever,headache,muscular ache etc.n2.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 featuren3.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 Diagnosisn1脑电图脑电图 弥漫性高波幅慢波弥漫性高波幅慢波 n2头颅头颅CT可正常，也可见一侧或双侧颞叶、可正常，也可见一侧或双侧颞叶、海马及边缘系统局灶性低密度区海马及边缘系统局灶性低密度区 n3脑脊液检查脑脊液检查压力及细胞数正常或轻度增压力及细胞数正常或轻度增高，重症者可明显增高。高，重症者可明显增高。n4脑脊液病原学检查脑脊液病原学检查对诊断颇有意义对诊断颇有意义 检检测测HSV抗原抗原 检测检测HSV特异性特异性lgM、lgG抗抗体体 CSF中中HSV-DNA（PCR快速诊断）快速诊断）n脑组织病理学及病原学检查脑组织病理学及病原学检查 HSE-Laboratory DiagnosisnEEG:lateralized high-voltage slow-waves.nCT scans show hypodensity of the affected areas.MRI shows signal changes in almost all.图1 图2 图3nCSF:increased pressure,lymphocytic pleocytosis,mild protein elevation and normal glucose.HSE-Laboratory DiagnosisnTests for the detection of HSV antigen in the CSF by the application of PCR are useful.nThe absolute way for dianosis:fluorecent antibody study and viral cultrue of cerebral tissue obtained by brain biopsy.HSE-diagnosis1临床临床诊断依据：诊断依据：口唇或生殖道口唇或生殖道疱疹疱疹史；史；高热、脑炎、精神症状高热、脑炎、精神症状三主征及局灶性神三主征及局灶性神经系统损害体经系统损害体征征；脑脊液脑脊液红、白细胞数增红、白细胞数增多多，糖和氯化物正常；糖和氯化物正常；脑电图脑电图以颞、额区以颞、额区损害为主的脑弥漫性异常；损害为主的脑弥漫性异常；头颅头颅CT或或MRI发现颞叶局灶性出血性脑软化灶；发现颞叶局灶性出血性脑软化灶；特特异性抗病毒药物治疗有效。异性抗病毒药物治疗有效。2.实验室实验室检查检查：CSF病原体病原体检查及检查及病理病理检查检查HSEDifferential diagnosisn急性播散性脑脊髓炎急性播散性脑脊髓炎：多在感染或疫苗接种：多在感染或疫苗接种后急性发病后急性发病 n结核性脑膜脑炎结核性脑膜脑炎：结核病病史或接触史结核病病史或接触史，慢慢性过程，性过程，脑膜刺激征脑膜刺激征是是TBM早早期表现期表现，可，可有有脑神经损害脑神经损害，CSF检查提示诊断检查提示诊断。n 肠道病毒性脑炎肠道病毒性脑炎：也是病毒性脑炎的常见：也是病毒性脑炎的常见病因之一，多见于夏秋季，可为流行性或散病因之一，多见于夏秋季，可为流行性或散发性发性 n带状疱疹病毒性脑炎带状疱疹病毒性脑炎 HSE-treatmentnAntiviral agentsnThere was no specific treatment for HVE untill the late 1970s acyclovir was introduced.nAcyclovir and ganciclovir are most effective drugs.They significantly reduce both the mortality and morbidity.HSE-treatmentn1抗病毒化学药物治疗抗病毒化学药物治疗 n(1)无环鸟苷无环鸟苷(阿昔洛韦阿昔洛韦,acyclovir)n(2)更昔洛韦更昔洛韦(ganciclovir)n2免疫治疗免疫治疗n干扰素及其诱生剂干扰素及其诱生剂 转移因子转移因子 肾上腺肾上腺皮质激素皮质激素n3全身支持治疗全身支持治疗 n4对症治疗对症治疗 Creutzfeldt-Jakob Disease nCreutzfeldt-Jakob病病(CJD)是最常见的人类是最常见的人类朊蛋朊蛋白病白病（具传染性的朊蛋白所致的散发性中枢神具传染性的朊蛋白所致的散发性中枢神经系统变性疾病）经系统变性疾病）n CJD is also called Subacute Spongiform Encephalopathy.(SSE)nIt belongs to the category called the transmissible spongiform encephalopathies(prion diseases)PrP and prion Protein deasen朊蛋白朊蛋白(prion protein,PrP)一种既一种既具有传具有传染性染性又又缺乏核酸缺乏核酸的非病毒性致病因子的非病毒性致病因子 nPrion 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 deasen人类朊蛋白病还有人类朊蛋白病还有 Kuru病病、Gerstmann-Straussler综合征综合征(GSS)、致死性家族性失眠症致死性家族性失眠症(FFI)、缺乏特缺乏特征性病理改变的征性病理改变的朊蛋白痴呆朊蛋白痴呆和伴痉和伴痉挛性截瘫的朊蛋白痴呆挛性截瘫的朊蛋白痴呆。What is CJD?nRefer to a distinctive 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.n The outstanding features of the neuropathologic changes are widespread neuronal loss and gliosis accompanied by a striking vacuolation or spongy state of the affected regionsCJD-Pathogenesis and Typen1型和型和2型存在于型存在于散发性散发性CJD(sporadicula CJD)n 3型型为为医源性医源性CJD-通过角膜、硬脑膜移植，通过角膜、硬脑膜移植，脑源性生物制品和埋藏未充分消毒的脑电极脑源性生物制品和埋藏未充分消毒的脑电极而传播而传播 Type-3:iatrogenic CJD by transplantation of corneas and implantation of infected depth electrdes etc.CJD-Pathogenesisn4型型是是新变异型新变异型-与疯牛病与疯牛病(MCD)具有相似具有相似的种系特异性的种系特异性n PrP基因突变形成基因突变形成遗传性家族型遗传性家族型CJD CJD-Pathologyn大体大体-脑呈脑呈海绵状改变，皮质、基海绵状改变，皮质、基底节和脊髓萎缩变性。底节和脊髓萎缩变性。nSpongy appearance shows in cerebral and cerebellar cortex.CJD-Pathology显微镜下显微镜下-神经元丢失、星形细胞增神经元丢失、星形细胞增生、生、细胞胞浆中空泡形成细胞胞浆中空泡形成，可发现，可发现感染组织内感染组织内异常异常PrP淀粉样斑块。淀粉样斑块。Widespread neuronal loss and gliosis accompanied by a striking vacuolation and PrPsc in the affected regions.CJD-临床表现临床表现 n1发病年龄发病年龄2578岁，平均岁，平均58岁，男女均可岁，男女均可罹患，新变异型平均罹患，新变异型平均26岁岁 n2隐袭起病，缓慢进行性发展隐袭起病，缓慢进行性发展n初期初期：表现颇似神经症，可有头痛、眩晕、：表现颇似神经症，可有头痛、眩晕、共济失调及视觉障共济失调及视觉障 碍等碍等 n中期中期：进行性痴呆进行性痴呆为主要表现，伴人格改变为主要表现，伴人格改变，有失语、偏瘫、锥体束征，有失语、偏瘫、锥体束征 或肌肉萎缩或肌肉萎缩 及及2/3病人出现病人出现肌阵挛，最具特征性肌阵挛，最具特征性 n晚期晚期：出现尿失禁、无动性缄默、昏迷：出现尿失禁、无动性缄默、昏迷 等等n3变异型变异型CJD临床表现共济失调和行为改临床表现共济失调和行为改变变 CJD-clinical featuren1.It occurs mostly in the late middle age,although can occur in young adult.n2.Progressive development.The early stage:AtypicalThe mid stage:gradual dementia with personality change.Myoclonus occurs in 2/3 of patients.The late stage:Coma,akinetic mutism.n3.Variant CJDCJD-Laboratory Findingn1免疫荧光检测免疫荧光检测CSF中中14-3-3蛋白蛋白可呈可呈阳性阳性-可疑可疑CJD病人重要指标。病人重要指标。血清血清S100蛋白蛋白（随病情进展呈持续性增高）。（随病情进展呈持续性增高）。n2脑电图：脑电图：疾病中晚期可出现疾病中晚期可出现间隔间隔0.52秒周期性棘秒周期性棘-慢复合波慢复合波。n3晚期晚期CT和和MRI：可见脑萎缩；可见脑萎缩；MRI显示双侧尾状核、壳核显示双侧尾状核、壳核T2呈对称性均质呈对称性均质高信号高信号，T1可完全正常可完全正常。CJD-Laboratory FindingnTest of CSF by immunoassay,the finding of 14-3-3 protein is very useful in separating SSE.Also is the serum P-100.nEEG:High voltage slow and sharp-wave complexes(0.5-2Hz).nMRI subtle hyperintensity of the lenticular nuclei on T2 weighted images when the disease is fully established.CJD-Diagnosis(诊断标准诊断标准)n很可能很可能(probable)CJD在在2年内发生的年内发生的进行性痴呆进行性痴呆；肌肌阵阵挛挛、视视力力障障碍碍、小小脑脑症症状状、无无动动性性缄缄默默等四项中具有其中两项；等四项中具有其中两项；脑电图周期性同步放电脑电图周期性同步放电的特征性改变。的特征性改变。n如如病病人人脑脑活活检检发发现现海海绵绵状状态态和和PrPSC者者，则为则为确诊的确诊的CJD。n可用脑蛋白检测代替脑电图特异性改变。可用脑蛋白检测代替脑电图特异性改变。CJD-DiagnosisnProbable SSE1)Progressive dementia in 2 years2)Two of myoclonus,visual disterbance,ataxia and akinetic mutism.3)EEG:synchronous discharge.nDefinite diagnosisSpongy or PRPsc is found by brain tissue biopsy.CJD-鉴别诊断鉴别诊断 nAlzheimer病病n进行性核上性麻痹进行性核上性麻痹n橄榄脑桥小脑萎缩橄榄脑桥小脑萎缩n脑囊虫病脑囊虫病n肌阵挛性癫等鉴别肌阵挛性癫等鉴别CJD-治疗及预后治疗及预后 n尚无有效治疗尚无有效治疗 n对症治疗对症治疗n巴氯芬巴氯芬(baclofen)治疗痉挛性张力增高，治疗痉挛性张力增高，n氯硝西泮氯硝西泮治疗肌阵挛，治疗肌阵挛，n痴痴呆呆可可用用三三乐乐喜喜、哌哌醋醋甲甲酯酯(利利他他林林)和和尼尼麦角林麦角林(脑通脑通)等。等。n应用反义寡核苷酸或基因治疗可能达到应用反义寡核苷酸或基因治疗可能达到治疗目的治疗目的 n90%病例于病后病例于病后1年内死亡年内死亡 脑囊虫病脑囊虫病Cerebral CysticercosisCerebral Cysticercosisn由由猪猪带带绦绦虫虫蚴蚴虫虫(囊囊尾尾蚴蚴)寄寄生生脑脑组组织形成包囊所致。织形成包囊所致。nCysticercosis is the larval stage(cysticercus)of infection with the pork tapeworm.Cerebral Cysticercosisn是是一一种种最最常常见见的的CNS寄寄生生虫虫感感染染，也也是是我我国国北北方方症症状状性性癫癫常常见见的的病病因之一。因之一。nCysticercosis is a leading cause of epilepsy and other neurologic disturbances.脑囊虫病脑囊虫病-病因及发病机制病因及发病机制 n最常见最常见的传播途径是摄入带有的传播途径是摄入带有虫卵污染虫卵污染的食物的食物 n少见少见原因为肛门原因为肛门-口腔转移而形成的口腔转移而形成的自身自身感染感染或者是绦虫的节片逆行入胃或者是绦虫的节片逆行入胃 n虫卵虫卵进入十二指肠内孵化逸出进入十二指肠内孵化逸出六钩蚴六钩蚴，蚴虫经血液循环分布全身并发育成蚴虫经血液循环分布全身并发育成囊尾囊尾蚴蚴，有不少囊尾蚴寄生在脑内。，有不少囊尾蚴寄生在脑内。脑囊虫病脑囊虫病-Pathologyn典型的包囊大小为典型的包囊大小为510mm，可有可有薄壁包膜，或呈多个囊腔薄壁包膜，或呈多个囊腔 The cysts may be 5-10mm.Thelesions are most often multiple but may be solitary.Cysticercosis-Pathologyn脑实质中包囊内存活的蚴虫很少引起脑实质中包囊内存活的蚴虫很少引起炎症，通常在感染后数年蚴虫死亡后炎症，通常在感染后数年蚴虫死亡后才出现明显的炎症反应才出现明显的炎症反应 Only when the cyst degenerated many months or years after the initial infestation,an inflammatory and granulomatous reaction is elicited and focal symptoms arise.脑囊虫病脑囊虫病-Clinical Featuren1脑实质型脑实质型 临床症状与包囊的位置有临床症状与包囊的位置有关关。n2蛛网膜型蛛网膜型 头痛、脑积水和虚性脑膜头痛、脑积水和虚性脑膜炎等。炎等。n3脑室型脑室型 阻塞性脑积水；阻塞性脑积水；布龙布龙(Brun)征发作征发作（移动的包囊，可突然阻塞第四（移动的包囊，可突然阻塞第四脑室正中孔，导致脑压突然增高，引起脑室正中孔，导致脑压突然增高，引起眩晕、呕吐、意识障碍和跌倒眩晕、呕吐、意识障碍和跌倒）。n4脊髓型脊髓型 非常罕见非常罕见 Clinical FeaturenThe cerebral manifestations of cysticercosis are diverse,related to the encystment and subsequent calcification of the larvae in cerebral parenchyma,subarachnoid space and ventricle.nThe flow of CSF may be obstructed by large subarachnoid or intraventricular cyst and leads to obstructive hydrocephalus.脑囊虫病脑囊虫病-Laboratory Diagnosisn1血常规血常规检查嗜酸性粒细胞增多。检查嗜酸性粒细胞增多。n2用用ELISA和和Western 印迹法检测印迹法检测血清血清囊虫抗体囊虫抗体常为常为阳性阳性。n3头颅头颅CT和和MRI可发现脑积水及被阻可发现脑积水及被阻塞的部位，塞的部位，CT可见单个或多个钙化点，可见单个或多个钙化点，CT平扫见包囊为小的透亮区，增强扫描平扫见包囊为小的透亮区，增强扫描为弥散性或环形增强影。为弥散性或环形增强影。Laboratory DiagnosisnCT or MRI may shows obstructive hydrocephalus.Enhancing cysts are easier found on MRI.Calcified cysts can be shown clearly on CT.nSerum test for immunoreaction of cysticercus is very useful.脑囊虫病脑囊虫病-Diagnosisn 曾居住在流行病区，并有曾居住在流行病区，并有癫痫、脑癫痫、脑膜炎或颅内压升高膜炎或颅内压升高表现的患者，应表现的患者，应疑及本病。疑及本病。Have ever been to the epidemic(en-demic)areas,with epilepsy,meningitis and the sign of high cranial pressure may be possible cysticecosis.脑囊虫病脑囊虫病-Diagnosis2.血清囊虫抗体试验血清囊虫抗体试验、皮下结节的囊、皮下结节的囊虫虫活检活检和头部和头部CT、MRI检查可帮助检查可帮助诊断。诊断。三脑室囊虫三脑室囊虫 外侧裂囊虫外侧裂囊虫Antibody test in serum and CSF and biopsy of subcuticular tubercle of cysticercus;together with CT and MRI are all very helpful.囊虫病巨大囊肿脑囊虫-Differential Diagnosisn脑肿瘤脑肿瘤n结核性脑膜炎结核性脑膜炎n其他病因所致的癫鉴别。其他病因所致的癫鉴别。脑囊虫病脑囊虫病-治疗治疗 n常用药物常用药物(antihelminthic)n吡喹酮吡喹酮(praziquantel)：是广谱抗寄是广谱抗寄生虫药，成人总剂量为生虫药，成人总剂量为300mg/kg。n阿苯哒唑阿苯哒唑(albendazole,丙硫咪唑丙硫咪唑)：广谱抗寄生虫药，成人总剂量亦为广谱抗寄生虫药，成人总剂量亦为300mg/kg。n用用药药过过程程中中必必须须严严密密监监测测，必必要要时时应应给给予予皮质类固醇或脱水剂皮质类固醇或脱水剂治疗。治疗。n单个病灶单个病灶(尤其是脑室内者尤其是脑室内者)可可手术手术摘除摘除。