细菌性脑膜炎

1、中枢神经系统感染性疾病浙江大学医学院从属邵逸夫医院神经内科 邵宇权第1页病例 现病史A 38-year-old woman was admitted to the hospital because of fever and confusionThe patient had been well until four days earlier, when a headache gradually developed and increased in intensity, accompanied by mild photophobia and stiffness of the neck. Two d

2、ays before admission, she believed that she was mildly febrile. The day before admission, she was examined at another facility, where she was told she had a “viral illness.” She was given fluids intravenously and was discharged. On the morning of admission, she awoke with shaking chills and a temper

3、ature of 40C. During the day she was aware of a rapid heartbeat, lightheadedness, and lethargy. Her husband observed that she was confused, and she was brought to this hospital and admitted.第2页病例 体检T 36.4, HR 99bpm, RR 20, BP90/60 mmHg. SaO2 99%The neck was rigid, and Kernigs sign (+)She was alert a

4、nd oriented but spoke in phrases of two to four words, rather than complete sentences. The neurologic examination otherwise revealed no abnormalities.第3页病例 辅助检验-CSF第一天第五天第4页病例 辅助检验-器械MRI showed a subtle hyperintensity on T2 images in both hippocampal regions and possible slight meningeal enhancement

5、. EEG revealed generalized low-amplitude slowing and continuous focal slowing over the entire left hemisphere; no epileptiform activity第5页病例 病情演变Shortly after the patients arrival at the hospital, T rose to 39.8, and the fever was accompanied by somnolenceOn the 2nd hospital day, T rose to 39.5. Whe

6、n questioned, she knew the month but not the date or year or the ages of her childrenLater on the 2nd day, she became more lethargic and responded to questions only with “yes.”During the night, the patients mental status improved and she was able to follow simple commandsOn the 3rd hospital day, the

7、 maximal T 39.2. The patient was more responsive to commands than she had been on the previous day, although she could not distinguish the right hand from the left.第6页定位诊疗定性诊疗诊疗依据怎样求证第7页定义、解剖和病原学病毒细菌真菌寄生虫螺旋体立克次体朊蛋白第8页细菌性脑膜炎化脓性脑膜炎非化脓性脑膜炎细菌：结核性脑膜炎非细菌：病毒性脑膜炎，隐球菌脑膜炎，螺旋体（神经莱姆病）等第9页化脓性脑膜炎病因和发病机制病理临床表现试验室检

8、验诊疗和判别诊疗治疗预后第10页化脓性脑膜炎-病因和发病机制发病率：1.5人/10万/年病原菌：成年人：肺炎链球菌（50%），脑膜炎双球菌（25%）儿童：流感嗜血杆菌（50%），脑膜炎双球菌（30%）新生儿：B组链球菌(50%)，大肠杆菌（20%）腰穿、脑室引流和颅脑手术：金葡、绿脓感染路径血行播散直接扩散经脑脊液第11页第12页化脓性脑膜炎-病理大致：大量脓性渗出物，血管扩张镜下：脑膜：炎细胞浸润蛛网膜下腔：中性粒细胞，纤维蛋白渗出物室管膜和脉络膜：炎细胞浸润，充血脑实质：偶见小脓肿第13页化脓性脑膜炎-临床表现头痛87%发烧77%颈强83%意识改变69%呕吐35%惊厥5%低温或发烧疲软思睡

9、易激惹高音调哭叫拒食、吸吮无力呕吐、腹泻囟门隆起（1/3)惊厥(40%)成人（包含大儿童）婴幼儿感染症状：寒战，发烧脑膜刺激征：颈强，克氏征，布氏征阳性颅内高压：头痛，呕吐，意识障碍局灶症状：偏瘫，失语其它症状：出血性皮疹第14页脑脊液检验血象头颅MR或CT脑电图其它：血培养、皮肤瘀点培养化脓性脑膜炎 试验室检验第15页诊疗：急性发病+三联征+脑脊液检验判别诊疗：病毒性脑膜炎结核性脑膜炎隐球菌性脑膜炎化脓性脑膜炎 诊疗和判别诊疗第16页化脓性脑膜炎 治疗：抗生素基本标准全程住院静脉给药足疗程选择标准肺炎球菌：头孢曲松+（万古霉素）脑膜炎双球菌：头孢曲松杆菌：绿脓（复达欣），其它（头孢曲松）李斯

10、特菌（氨苄青）；金葡（万古霉素）未确定病原菌：头孢曲松第17页激素：地塞米松10-20mg/d3-5天补液和脱水发烧惊厥脑积水隔离化脓性脑膜炎治疗：其它第18页化脓性脑膜炎 预后病死率15%后遗症：智力减退癫痫脑积水第19页结核性脑膜炎病因和发病机制病理临床表现试验室检验诊疗和判别诊疗治疗预后第20页结核性脑膜炎发病率0.35-0.7/10万/年第21页结核性脑膜炎 病因和发病机制病原菌人型结核分枝杆菌牛型结核分枝杆菌感染路径血行播散淋巴系统播散局部播散第22页结核性脑膜炎 病理脑底部渗出物血管炎脑积水第23页结核性脑膜炎 临床表现慢性、亚急性、急性脑膜炎共有症状颅高压脑膜刺激征结核菌相对有特

11、点症状毒血症状：低热、盗汗、纳差、乏力、精神软脑神经损害脑室质损害第24页结核性脑膜炎 辅助检验金标准：抗酸染色，结核菌培养新方法：PCR、ADA、免疫组化、酶联免疫脑脊液：常规、生化影像学：胸片/CT，脑CT/MRI其它：PPD皮试，血沉，血常规第25页结核性脑膜炎 Ahuja诊疗标准A临床：发烧头痛14天（必须）；呕吐/局灶缺失症状（不是必须）B脑脊液：1细胞数20（淋巴60%），2蛋白100mg/dl，糖60%血糖，3墨汁染色（-），肿瘤细胞（-）C影像学：有以下2项或以上：1基底池和外侧裂渗出物；2脑积水；3脑梗塞；4脑回强化D颅外结核确诊TBM：A+找到结核杆菌或尸解100%高度可能

12、TBM：A+B+C+D91.7% 很可能TBM：A+(B+C+D)中2个66.7%可能TBM：A+（B+C+D）中1个38.5%阳性预测值（PPV）第26页结核性脑膜炎 诊疗新方法Sensitivity and specificity of immunocytochemical staining of mycobacterial antigens in the cytoplasm of cerebrospinal fluid macrophages for diagnosing tuberculous meningitis. Shao Y, Xia P, Zhu T, Hu X.J Clin

13、Microbiol. Sep;49(9):3388-91.第27页结核性脑膜炎 判别诊疗化脓性脑膜炎病毒性脑膜炎隐球菌性脑膜炎脑膜癌病第28页结核性脑膜炎 治疗抗痨治疗药品种类：异烟肼(H)、利福平(R)、吡嗪酰胺(Z)、乙胺丁醇(E)、链霉素(S)适用方案和疗程：惯用（HRZ），耐药加E/S副作用和监测：肝酶激素：指证对症：脱水降颅压、抗癫痫、脑积水引流术第29页结核性脑膜炎 预后自然病程6-8周死亡合理治疗90%恢复，但25%有后遗症婴幼儿和老年人预后差入院时意识障碍、颅神经损害、脑脊液蛋白浓度高预后差其它脏器结核或粟粒性结核不影响预后后遗症轻重不一第30页单纯疱疹病毒性脑炎病因和发病机制

14、病理临床表现试验室检验诊疗和判别诊疗治疗预后第31页单疱脑炎 病因和发病机制发病率4-8/10万单纯疱疹病毒（HSV）I型（90%），II型（10%）路径：HSV-1：亲密接触、飞沫 （三叉神经节）HSV-2：性接触、母婴 （骶神经节）病机：病毒直接损害：HSV-1致细胞凋亡，HSV-2无免疫介导损害第32页单疱脑炎 病理部位出血坏死炎性包涵体第33页单疱脑炎 临床表现脑实质症状精神行为异常、认知障碍癫痫发作意识障碍局灶症状感染症状前驱症状：上感、疱疹第34页单疱脑炎 试验室检验脑电图影像学脑脊液病原学病理第35页单疱脑炎 诊疗临床拟诊临床表现：前驱、感染症状、脑实质症状脑脊液脑电图影像学确诊PCR双份CSF发觉HSV特异性抗体改变脑活检第36页单疱脑炎 判别诊疗其它病毒性脑炎带状疱疹病毒巨细胞病毒性乙型病毒腮腺炎病毒麻疹病毒急性播散性脑脊髓炎（ADEM）第37页单疱脑炎 治疗抗病毒治疗早期、按时、足疗程阿昔洛韦，更昔洛韦激素对症治疗抗癫痫降温治疗精神症状降颅压第38页单疱脑炎 预后不治疗死亡率70-80%，阿昔洛韦治疗后降至28%预后取决于意识情况患者年纪治疗是否及时后遗症10%第39页回到原来病例第40页定位依据头痛、颈强、克氏