中枢神经系统感染(2)课件

1、中枢神经系统感染(2)1 VIRAL MENINGITIS 轴突传播轴突传播：neuronal spread of the virus by axonal transport (eg, herpes simplex, rabies狂犬病病毒狂犬病病毒); 1. 自身免疫性感染后脱髓鞘自身免疫性感染后脱髓鞘：autoimmune postinfections demyelination脱髓鞘脱髓鞘 (eg, varicella水痘病毒水痘病毒, influenza). 中枢神经系统感染(2)7 Pathologic changes in viral meningitis consist of a

2、n inflammatory meningeal reaction mediated by lymphocytes. 病毒性脑膜炎的病理改变是由淋巴细胞介导的病毒性脑膜炎的病理改变是由淋巴细胞介导的 炎性脑膜反应。炎性脑膜反应。 中枢神经系统感染(2)8 Encephalitis is characterized by perivascular cuffing, lymphocytic infiltration, and microglial proliferation mainly involving subcortical gray matter regions. Internuclear

3、 or intracytoplasmic inclusions are often seen. 病毒性脑炎的病理改变特点是血管周围套袖样病毒性脑炎的病理改变特点是血管周围套袖样 改变、淋巴细胞浸润，以及累及皮层下灰质的改变、淋巴细胞浸润，以及累及皮层下灰质的 小胶质增生，并经常可见到核浆或细胞浆内包小胶质增生，并经常可见到核浆或细胞浆内包 涵体。涵体。 中枢神经系统感染(2)9 Clinical findings- symptoms and signs Clinical manifestations include fever, headache, neck stiffness, photop

4、hobia畏光畏光, pain with eye movement, and mild impairment of consciousness. Patients usually do not appear as ill as those with bacterial meningitis. Systemic viral infection may cause skin rash, pharyngitis咽炎咽炎, lymphadenopathy淋巴结病淋巴结病, pleuritis胸胸 膜炎膜炎, carditis心肌炎心肌炎, jaundice黄疸黄疸, organomegaly器官肿大器

5、官肿大, diarrhea腹泻腹泻, or orchitis睾丸炎睾丸炎, and these findings may suggest a particular etiologic agent病原体病原体. 中枢神经系统感染(2)10 Because viral encephalitis involves the brain directly, marked alterations of consciousness, seizures, and focal neurologic signs can occur. When signs of meningeal irritation 脑膜刺激征

6、脑膜刺激征and brain dysfunction coexist共存共存, the condition is termed meningoencephalitis脑膜脑炎脑膜脑炎. 中枢神经系统感染(2)11 中枢神经系统感染(2)12 Laboratory findings CSF analysis is the most important laboratory test. CSF pressure is normal or increased a lymphocytic or monocytic pleocytosis脑脊液细胞数增多脑脊液细胞数增多 is present, with

7、 cell counts usually less than 1000/ml. (higher counts can be seen in lymphocytic choriomeningitis脉络丛脑膜炎脉络丛脑膜炎 or herpes simplex encephalitis.) A polymorphonuclear多形核白细胞多形核白细胞 pleocytosis can occur early in viral meningitis, while red blood cells may be seen with herpes simplex encephalitis. 中枢神经系统感

8、染(2)13 Protein is normal or slightly increased (usually 80120mg/dL). Glucose is usually normal, but may be decreased in mumps腮腺炎腮腺炎, herpes zoster 带状疱疹带状疱疹, or herpes simplex encephalitis. Grams stain and bacterial, fungal, and acid-fast bacillius(AFB) cultures are negative. Oligoclonal bands寡克隆区带寡克

9、隆区带and CSF protein electrophoresis电泳电泳abnormalities may be present. An etiologic diagnosis can often be made by virus isolation, polymerase chain reaction, or acute- and convalescent phase恢复期恢复期CSF antibody titers抗体滴度抗体滴度. 中枢神经系统感染(2)14 Blood counts may show a normal white cell count, leukopenia白血球减

10、少白血球减少 症症, or mild leukocytosis白细胞增多白细胞增多. Serum amylase血清淀粉酶血清淀粉酶is frequently elevated in mumps 腮腺炎腮腺炎; abnormal liver function tests are associated with both hepatitis viruses肝炎病毒肝炎病毒and infectious mononucleosis单核细胞增多症单核细胞增多症. 中枢神经系统感染(2)15 The EEG is diffusely slow, especially if there is direct

11、 cerebral involvement. 中枢神经系统感染(2)16 Diagnosis 中枢神经系统感染(2)17 Differential diagnosis The differential diagnosis of meningitis with mononuclear cell pleocytosis includes partially treated bacterial meningitis治疗不彻底治疗不彻底 的细菌性脑膜的细菌性脑膜炎 as well as syphilitic梅毒梅毒 的, tuberculous结核性结核性的, fungal, parasitic寄生物

12、寄生物的, neoplastic肿瘤肿瘤的, and other meningitides脑脑(脊脊)膜膜炎. 中枢神经系统感染(2)18 Evidence of systemic viral infection and CSF wet mounts, stained smears, cultures, and cytologic examination细胞学检查细胞学检查can distinguish among these possibilities. When presumed early viral meningitis is associated with a polymorphon

13、uclear多形核白细胞多形核白细胞 pleocytosis of less than 1000 white blood cells/mL and normal CSF glucose, one of two strategies can be used. 中枢神经系统感染(2)19 The paitent can be treated for bacterial meningitis until the results of CSF cultures are known; Treatment can be withheld and lumbar puncture腰椎穿刺术腰椎穿刺术 repe

14、ated in 612 hours. If the meningitis is viral in origin, the second sample should show a mononuclear cell pleocytosis. 中枢神经系统感染(2)20 A disorder that may be clinically indistinguishable from viral encephalitis is the immune- mediated encephalomyelitis that may follow viral infections such as influenz

15、a, measles麻疹麻疹, or chickenpox水痘水痘. Progressive neurologic disfunction typically begins a few days after the viral illness, but can also occur either simultaneously同时发生同时发生 or up to several weeks later. 中枢神经系统感染(2)21 Neurologic abnormalities result from perivenous 静脉周围的静脉周围的 demyelination脱髓鞘脱髓鞘, with

16、 often severely affects the brainstem. The CSF shows a lymphocytic pleocytosis脑脊液细胞数增多脑脊液细胞数增多, usually with cell counts of 50150/mL, and mild protein elevation. 中枢神经系统感染(2)22 Treatment Except for herpes simplex encephalitis, which is discussed separately no specific therapy for viral meningitis and

17、 encephalitis is available. Corticosteroids are of no proven benefit except in immune- mediated postinfectious syndromes. 中枢神经系统感染(2)23 Headache and fever can be treated with acetaminophen醋氨酚醋氨酚, but aspirin should be avoided, especially in children and young adults, because of its association with

18、Reyes syndrome. Seizures usually respond to phenytoin 苯妥英钠苯妥英钠or phenobarbital苯苯 巴比妥巴比妥. Supportive measures in comatose昏昏 睡的睡的patients include mechanical ventilation and intravenous or nasogastric feeding鼻饲鼻饲. 中枢神经系统感染(2)24 Prognosis Symptoms of viral meningitis usually resolve spontaneously within

19、 2 weeks regardless of the causative agent, although residual deficits后遗症后遗症may be seen. The outcome of viral encephalitis varies with the specific virus -for example, herpes simplex virus infections are associated with severe morbidity and high mortality rates. Mortality rates as high as 20% have a

20、lso been reported in immune- mediated encephalomyelitis脑脊髓炎脑脊髓炎 following measles麻疹麻疹 infections. 中枢神经系统感染(2)25 Herpes simplex virus (HSV) encephalitis 中枢神经系统感染(2)26 HSV is the most common cause of sporadic散发的散发的 fatal encephalitis in the United States. About two-thirds of cases patients over 40 yea

21、rs of age. Primary herpes infections most often present as stomatitis口炎口炎 ( HSV type 1) or a venereally 性交性交 的的transmitted genital生殖器生殖器eruption 出疹出疹 (HSV tpye 2). 中枢神经系统感染(2)27 The virus migrates along nerve axons轴突轴突to sensory ganglia神经节神经节, where it persists in a latent form and may be subsequent

22、ly reactivated. It is not clear whether HSV type 1 encephalitis, the most common type in adults, represents a primary infection or a reactivation of latent infection. 中枢神经系统感染(2)28 Neonatal新生儿的新生儿的HSV encephaltis usually results from acquisition获得获得 of type 2 virus during passage through the brith c

23、anal of a mother with active genital生殖器的生殖器的 lesions. Central nervous system involvement by HSV type 2 in adults usually causes meningitis, rather than encephalitis. 中枢神经系统感染(2)29 Pathology HSV tpye 1 encephalitis is an acute, necrotizing引坏死的引坏死的, asymmetric不对称的不对称的hemorrhagic出血性出血性 的的process with l

24、ymphocytic and plasma cell浆细胞浆细胞reaction. Usually involves the medial temporal and inferior frontal lobes. Intranuclear inclusions核内包涵体核内包涵体may be seen in neurons神经元神经元and glia神经神经 胶质胶质. Patients who recover康复期康复期 may show cystic囊的囊的necrosis坏死坏死of the involved regions. 中枢神经系统感染(2)30 中枢神经系统感染(2)31 中枢

25、神经系统感染(2)32 中枢神经系统感染(2)33 嗜酸性嗜酸性Cowdry A型包涵体型包涵体 中枢神经系统感染(2)34 Clinical Finding- A Symptoms and Signs The clinical syndrome may include headache, stiff neck, vomiting, behavioral disorders, memory loss, anosmia嗅觉丧失嗅觉丧失, aphasia, hemiparesis轻偏瘫轻偏瘫, and focal or generalized seizures. 中枢神经系统感染(2)35 Act

26、ive herpes labialis唇疱疹唇疱疹is seen occasionally, but does not reliably implicate HSV as the cause of encephalitis. 中枢神经系统感染(2)36 HSV encephalitis is uaually rapidly progressive over several days and may result in coma or death. The most common sequelae 后遗症后遗症 in patients who survive are memory and beh

27、avior disturbances, reflecting the predilection 嗜好嗜好, 偏爱偏爱of HSV for limbic structures. 中枢神经系统感染(2)37 Laboratory Findings 中枢神经系统感染(2)38 Laboratory Findings-CSF The CSF in HSV tpye 1 encephalitis most often shows increased pressure lymphocytic or mixed lymphocytic and polymorphonuclear多形核白细胞多形核白细胞 pl

28、eocytosis( 50100 white blood cells/mL) mild protein elevation, and normal glucose. Red blood cells, xanthochromia 黄变黄变, and decreased glucose are seen in some cases. 中枢神经系统感染(2)39 Laboratory Findings- VIRUS The virus generally cannot be isolated from the CSF, but viral DNA has been detected by the p

29、olymerase chain reaction聚合酶链反应聚合酶链反应 in some cases. 中枢神经系统感染(2)40 HSV抗体检定 ELASA是现今国际上通用的HSV抗体检测方 法。 本方法采用双份血清和双份脑脊液作HSV-1 抗体的动态检测。 诊断标准： 双份CSF抗体有增高趋势，滴度1:8以上； 双份CSF抗体4倍以上升高； 血与CSF的抗体比值40。 中枢神经系统感染(2)41 Laboratory Findings-EEG The EEG may show periodic周期的周期的 slow-wave complexes arising from one or bo

30、th temporal lobes 中枢神经系统感染(2)42 Laboratory Findings- CT MRI CT scans and MRI may show abnormalities in one or both temporal lobes. These can extend to frontal or parietal regions顶区顶区 and are sometimes enhanced with the infusion注入注入of contrast material 造影剂造影剂. However, imaging studies may also be nor

31、mal. 中枢神经系统感染(2)43 中枢神经系统感染(2)44 中枢神经系统感染(2)45 中枢神经系统感染(2)46 中枢神经系统感染(2)47 Diagnosis 中枢神经系统感染(2)48 中枢神经系统感染(2)49 中枢神经系统感染(2)50 中枢神经系统感染(2)51 Differential Diagnosis The symptoms and signs are not specific for herpes virus infection. The greatest diagnostic difficulty is distinguishing between HSV enc

32、ephalitis and brain abscess脑脓肿脑脓肿, and the tow disorders often cannot be differentiated on clinical grounds alone. 中枢神经系统感染(2)52 brain abscess 中枢神经系统感染(2)53 brain abscess 中枢神经系统感染(2)54 Other CNS infections and vasculitis血管炎血管炎 can also mimic HSV encephalitis. Deginitive diagnosis can be made by biopsy of affected brain areas, with the choice of biopsy site guided by the EEG, CT, or MRI findings. Ho