中枢神经系统感染1

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1、VIRAL MENINGITIS&ENCEPHALITIS Viral meningitis refers to meningitis caused by a viral infection.Children and young adults are frequently affected.Viral meningitis is most often caused by enteric 肠道的肠道的viruses Viral encephalitis by childhood exanthems皮疹皮疹,arthropod-borne节肢节肢动物动物agents虫媒性病原体虫媒性病原体,and

2、 herpes simplex type 1.Cause最常见最常见 柯萨奇病毒柯萨奇病毒 ECHO病毒病毒 肠道病毒肠道病毒其次其次流行性腮腺炎流行性腮腺炎单纯疱疹病毒单纯疱疹病毒腺病毒腺病毒PathologyViral infections can affect the central nervous system in three ways1.血源性播散血源性播散：hematogenous dissemination of a systemic viral infection(eg,arthropod-borne viruses虫媒性病毒虫媒性病毒);2.轴突传播轴突传播：neurona

3、l spread of the virus by axonal transport(eg,herpes simplex,rabies狂犬病病毒狂犬病病毒);3.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).Pathologic changes in viral meningitis consist of an inflammatory meningeal reaction mediated by lymphocytes.病毒性脑膜炎的病理改

4、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。Encephalitis is characterized by perivascular cuffing,lymphocytic infiltration,and microglial proliferation mainly involving subcortical gray matter regions.Internuclear 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

5、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。Clinical findings-symptoms and signs Clinical manifestations include fever,headache,neck stiffness,photophobia畏光畏光,pain with eye movement,and mild impairment of consciousness.Patients usually do not appear as ill a

6、s 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.Because viral encep

7、halitis 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.Laboratory findingsCSF analysis is the most importan

8、t laboratory test.CSF pressure is normal or increaseda lymphocytic or monocytic pleocytosis脑脊液细胞数增多脑脊液细胞数增多 is present,with 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 pleo

9、cytosis can occur early in viral meningitis,while red blood cells may be seen with herpes simplex encephalitis.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 an

10、d bacterial,fungal,and acid-fast bacillius(AFB)cultures are negative.Oligoclonal bands寡克隆区带寡克隆区带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 tite

11、rs抗体滴度抗体滴度.Blood counts may show a normal white cell count,leukopenia白血球减少白血球减少症症,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.Th

12、e EEG is diffusely slow,especially if there is direct cerebral involvement.DiagnosisDifferential diagnosis The differential diagnosis of meningitis with mononuclear cell pleocytosis includes partially treated bacterial meningitis治疗不彻治疗不彻底的细菌性脑膜炎底的细菌性脑膜炎 as well as syphilitic梅毒梅毒的的,tuberculous结核性的结核性

13、的,fungal,parasitic寄生物的寄生物的,neoplastic肿瘤的肿瘤的,and other meningitides脑脑(脊脊)膜炎膜炎.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 polymorp

14、honuclear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.1.The paitent can be treated for bacterial meningitis until the results of CSF cultures are known;2.Treatment can be withheld and lumbar puncture腰椎穿刺术腰椎穿刺术 repeated in 612

15、 hours.If the meningitis is viral in origin,the second sample should show a mononuclear cell pleocytosis.A disorder that may be clinically indistinguishable from viral encephalitis is the immune-mediated encephalomyelitis that may follow viral infections such as influenza,measles麻疹麻疹,or chickenpox水痘

16、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.Neurologic abnormalities result from perivenous 静脉周围的静脉周围的demyelination脱髓鞘脱髓鞘,with often severely affects the brainstem.The CSF show

17、s 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.Treatment Except for herpes simplex encephalitis,which is discussed separately no specific therapy for viral meningitis and encephalitis is available.Corticosteroids are of no proven benefit e

18、xcept in immune-mediated postinfectious syndromes.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 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.Sup

19、portive measures in comatose昏昏睡的睡的patients include mechanical ventilation and intravenous or nasogastric feeding鼻饲鼻饲.Prognosis Symptoms of viral meningitis usually resolve spontaneously within 2 weeks regardless of the causative agent,although residual deficits后遗症后遗症may be seen.The outcome of viral

20、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 also been reported in immune-mediated encephalomyelitis脑脊髓炎脑脊髓炎following measles麻疹麻疹 infections.Herpes simplex viru

21、s(HSV)encephalitis 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 years 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

22、tpye 2).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 subsequently 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.Neonatal

23、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 canal 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.Pathology HSV tpye 1 encepha

24、litis 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 lymphocytic 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 m

25、ay show cystic囊的囊的necrosis坏死坏死of the involved regions.嗜酸性嗜酸性Cowdry A型包涵体型包涵体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.Active herpes

26、labialis唇疱疹唇疱疹is seen occasionally,but does not reliably implicate HSV as the cause of encephalitis.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 behavior disturbances,reflectin

27、g the predilection 嗜好嗜好,偏爱偏爱of HSV for limbic structures.Laboratory FindingsLaboratory 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 pleocytosis(50100 white blood cells/mL)mild protein elevation,

28、and normal glucose.Red blood cells,xanthochromia 黄变黄变,and decreased glucose are seen in some cases.Laboratory Findings-VIRUS The virus generally cannot be isolated from the CSF,but viral DNA has been detected by the polymerase chain reaction聚合酶链反应聚合酶链反应in some cases.HSV抗体检定 ELASA是现今国际上通用的HSV抗体检测方法。本

29、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。Laboratory Findings-EEG The EEG may show periodic周期的周期的slow-wave complexes arising from one or both temporal lobesLaboratory Findings-CT MRI CT scans and MRI may show abnormalities in one or both temporal lobes.These ca

30、n 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 normal.DiagnosisDifferential Diagnosis The symptoms and signs are not specific for herpes virus infection.The greatest diagnostic difficulty is di

31、stinguishing between HSV encephalitis and brain abscess脑脓肿脑脓肿,and the tow disorders often cannot be differentiated on clinical grounds alone.brain abscessbrain abscess 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 brai

32、n areas,with the choice of biopsy site guided by the EEG,CT,or MRI findings.However,because treatment is most effective when begun early and is comparatively safe,the most common approach is to treat patients with possible HSV encephalitis as described below and to reserve biopsy for those who fail

33、to improve.Treatment The most effective drug is acyclovir阿昔洛韦阿昔洛韦 Given intravenously at a dosage of 1015mg/kg every 8 hours,with each dose given over 1 hour.Treatment is continued for 1421 days.Complications include erythema红斑红斑at the infusion site,gastrointestinal 胃肠道胃肠道disturbances,headache,skin

34、rash,tremor,seizures,and encephalopathy脑病脑病or coma.Treatment is started as early as possible,since outcome is greatly influenced by the severity of dysfunction at the time treatment is initiated.肾上腺皮质激素肾上腺皮质激素 地塞米松地塞米松 甲泼尼龙甲泼尼龙Prognosis Patients under the age of 30 years and those who are only lethargic昏昏睡的睡的at the onset of treatment are more likely to survive than are older or comatose patients.The mortality rate is about 25%at 18 months in patients given acyclovir阿昔洛韦阿昔洛韦.