《神经病学》（英文）课件6.Infections of the CNS

1、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 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 vessel

2、lead to acute and subacute infections.第一节 概述分类： 感染的部位 ；发病情况及病程 ；特异性致病因子 CNS感染途径(pathway of infection)hematogenous spread；direct infection ；Peripheral nerves pathwayCNS病毒感染性疾病新的认识 第二节 病毒感染性疾病 Viral infections of CNS单纯疱疹病毒性脑炎Herpes Simplex Encephalitis Creutzfeldt-Jakob DiseaseHerpes Simplex Encephali

3、tis 病因及发病机制( Causes and Mechanisms)病理（pathology) 临床表现 (Clinical features)辅助检查 (laboratory finding)诊断及鉴别诊断 (Diagnosis and Differential Diagnosis)治疗（treatment) HSE-Causes and MechanismsHSV-嗜神经(neurotropic )DNA病毒 90%的人类HSE是由I型引起 70%HSE起因于内源性病毒的活化 (复发性疱疹感染 )25%的病例是原发感染 (口腔和呼吸道 )6%15%系由II型所致 (产妇生殖道HSV-II

4、原发感染 )绝大多数新生儿的HSE系HSV-II引起 HSE- Pathology颞叶、额叶等部位出血性坏死 |、渗出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-PathologyCowdry A型包涵体 (A type inclusion body)存在于病灶边缘的部分神经细胞核内 及星型细胞和少突胶质细胞核内。 HSE- Clinic

5、al feature1任何年龄、季节均可发病原发感染的潜伏期为221天，平均6天；前驱期症状2病程 多急性起病 ，口唇疱疹史 （1/4），高热，首发症状 ：头痛、轻微的意识和人格改变 或全身性或部分性运动性发作 ；病情缓慢进展精神症状表现突出智能障碍也较明显 3 神经症状 局灶性脑损害 ；脑膜刺激征 ；意识障碍 ；全身性或部分性癫痫 。重症脑疝形成而死亡 （死亡率高达40%70% ）。HSE-Clinical feature1.It occurs sporadically throughout the year and in patients of all ages. During prodr

6、omal 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 feature3.Neurologic symptom an

7、d sign hemiparesis,aphasia,meningeal rritatioin,disorder of conciousness,focal or generalized seizures.It may result in coma or death in some cases.HSE- Laboratory Diagnosis1脑电图 弥漫性高波幅慢波 2头颅CT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 3脑脊液检查压力及细胞数正常或轻度增高，重症者可明显增高。4脑脊液病原学检查对诊断颇有意义 检测HSV抗原 检测HSV特异性lgM、lgG抗体 CSF中HS

8、V-DNA（PCR快速诊断）脑组织病理学及病原学检查 HSE-Laboratory DiagnosisEEG:lateralized high-voltage slow-waves.CT scans show hypodensity of the affected areas. MRI shows signal changes in almost all. 图1 图2 图3CSF:increased pressure, lymphocytic pleocytosis, mild protein elevation and normal glucose.HSE-Laboratory Diagno

9、sisTests 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-diagnosis1临床诊断依据：口唇或生殖道疱疹史；高热、脑炎、精神症状三主征及局灶性神经系统损害体征；脑脊液红、白细胞数增多，糖和氯化物正常；脑电图以颞、额区损害为主的脑

10、弥漫性异常；头颅CT或MRI发现颞叶局灶性出血性脑软化灶；特异性抗病毒药物治疗有效。2. 实验室检查 ：CSF病原体检查及病理检查HSEDifferential diagnosis急性播散性脑脊髓炎：多在感染或疫苗接种后急性发病 结核性脑膜脑炎：结核病病史或接触史，慢性过程，脑膜刺激征是TBM早期表现 ，可有脑神经损害，CSF检查提示诊断 。 肠道病毒性脑炎：也是病毒性脑炎的常见病因之一，多见于夏秋季，可为流行性或散发性 带状疱疹病毒性脑炎 HSE -treatmentAntiviral agentsThere was no specific treatment for HVE untill

11、the late 1970s acyclovir was introduced.Acyclovir and ganciclovir are most effective drugs.They significantly reduce both the mortality and morbidity.HSE- treatment1抗病毒化学药物治疗 (1) 无环鸟苷 (阿昔洛韦, acyclovir) (2) 更昔洛韦(ganciclovir) 2免疫治疗干扰素及其诱生剂 转移因子 肾上腺皮质激素3全身支持治疗 4对症治疗 Creutzfeldt-Jakob Disease Creutzfeld

12、t-Jakob病 (CJD)是最常见的人类朊蛋白病 （具传染性的朊蛋白所致的散发性中枢神经系统变性疾病） 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)一种既具有传染性又缺乏核酸的非病毒性致病因子 Prion is neither a

13、 virus nor a viroid(nucleic acid alone,without a capsid structure)but the conversion of a normal cellular protein.PrP and prion Protein dease人类朊蛋白病还有 Kuru病、Gerstmann-Straussler综合征(GSS)、致死性家族性失眠症(FFI)、缺乏特征性病理改变的朊蛋白痴呆和伴痉挛性截瘫的朊蛋白痴呆 。What is CJD?Refer to a distinctive cerebral disease in which a rapidly

14、 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 accompanied by a striking vacuolation or spongy st

15、ate of the affected regionsCJD- Pathogenesis and Type1型和2型存在于散发性CJD(sporadicula CJD ) 3型为医源性CJD-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而传播 Type-3:iatrogenic CJD by transplantation of corneas and implantation of infected depth electrdes etc.CJD- Pathogenesis4型是新变异型-与疯牛病(MCD)具有相似的种系特异性 PrP基因突变形成遗传性家族型CJD CJD-

16、Pathology大体-脑呈海绵状改变，皮质、基底节和脊髓萎缩变性。Spongy appearance shows in cerebral and cerebellar cortex. CJD -Pathology显微镜下-神经元丢失、星形细胞增生、细胞胞浆中空泡形成，可发现感染组织内异常PrP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 1发病年龄2578岁，平均58岁，男女均可罹患，新变异

17、型平均26岁 2隐袭起病，缓慢进行性发展初期：表现颇似神经症，可有头痛、眩晕、共济失调及视觉障 碍等 中期：进行性痴呆为主要表现，伴人格改变 ，有失语、偏瘫、锥体束征 或肌肉萎缩 及2/3病人出现肌阵挛，最具特征性 晚期：出现尿失禁、无动性缄默、昏迷 等3变异型CJD临床表现共济失调和行为改变 CJD-clinical feature1. It occurs mostly in the late middle age, although can occur in young adult.2. Progressive development.The early stage: AtypicalTh

18、e mid stage: gradual dementia with personality change. Myoclonus occurs in 2/3 of patients.The late stage : Coma, akinetic mutism.3. Variant CJDCJD- Laboratory Finding1免疫荧光检测CSF中14-3-3蛋白可呈阳性 -可疑CJD病人重要指标。血清S100蛋白（随病情进展呈持续性增高）。2脑电图：疾病中晚期可出现间隔0.52秒周期性棘-慢复合波。 3晚期CT和MRI：可见脑萎缩；MRI显示双侧尾状核、壳核T2呈对称性均质高信号 ，T

19、1可完全正常 。CJD-Laboratory FindingTest 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 lenticular nuclei on T2 weighted images when the disease is full

20、y established.CJD- Diagnosis(诊断标准)很可能(probable) CJD在2年内发生的进行性痴呆；肌阵挛、视力障碍、小脑症状、无动性缄默等四项中具有其中两项；脑电图周期性同步放电的特征性改变。如病人脑活检发现海绵状态和PrPSC者，则为确诊的CJD。可用脑蛋白检测代替脑电图特异性改变。CJD-DiagnosisProbable SSE1)Progressive dementia in 2 years2)Two of myoclonus, visual disterbance, ataxia and akinetic mutism.3)EEG: synchronou

21、s discharge.Definite diagnosisSpongy or PRPsc is found by brain tissue biopsy.CJD-鉴别诊断 Alzheimer病进行性核上性麻痹橄榄脑桥小脑萎缩脑囊虫病肌阵挛性癫等鉴别CJD-治疗及预后 尚无有效治疗 对症治疗巴氯芬(baclofen)治疗痉挛性张力增高，氯硝西泮治疗肌阵挛，痴呆可用三乐喜、哌醋甲酯(利他林)和尼麦角林(脑通)等。应用反义寡核苷酸或基因治疗可能达到治疗目的 90%病例于病后1年内死亡 脑囊虫病Cerebral CysticercosisCerebral Cysticercosis由猪带绦虫蚴虫(囊

22、尾蚴)寄生脑组织形成包囊所致。Cysticercosis is the larval stage (cysticercus) of infection with the pork tapeworm.Cerebral Cysticercosis是一种最常见的CNS寄生虫感染，也是我国北方症状性癫常见的病因之一。Cysticercosis is a leading cause of epilepsy and other neurologic disturbances.脑囊虫病-病因及发病机制 最常见的传播途径是摄入带有虫卵污染的食物 少见原因为肛门-口腔转移而形成的自身感染或者是绦虫的节片逆行入胃

23、 虫卵进入十二指肠内孵化逸出六钩蚴，蚴虫经血液循环分布全身并发育成囊尾蚴，有不少囊尾蚴寄生在脑内。 脑囊虫病- Pathology典型的包囊大小为510mm，可有薄壁包膜，或呈多个囊腔 The cysts may be 5-10mm.Thelesions are most often multiple but may be solitary.Cysticercosis -Pathology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才出现明显的炎症反应 Only when the cyst degenerated many months or years after the

24、 initial infestation, an inflammatory and granulomatous reaction is elicited and focal symptoms arise.脑囊虫病- Clinical Feature1脑实质型 临床症状与包囊的位置有关 。2蛛网膜型 头痛、脑积水和虚性脑膜炎等。3脑室型 阻塞性脑积水；布龙(Brun)征发作（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，引起眩晕、呕吐、意识障碍和跌倒 ） 。4脊髓型 非常罕见 Clinical FeatureThe cerebral manifestations of cysticer

25、cosis 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.脑囊虫病- Laboratory Diagnosis1血常规检查嗜酸性粒细胞增多。 2用ELISA和Western 印迹法检测血清囊虫抗体常为阳性。 3头颅CT和MRI可发现脑积水及被阻塞的部位，CT可见单个或多个钙化点，CT平扫见包囊为小