1、中枢神经系统感染性疾病浙江大学医学院附属邵逸夫医院浙江大学医学院附属邵逸夫医院神经内科神经内科 邵宇权邵宇权病例病例 现病史现病史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 stiffne
2、ss of the neck.Two days 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
3、and a temperature 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.病例病例 体检体检T 36.4,HR 99bpm,RR 20,BP90/60 mmHg.SaO2 99%The neck was rigid,and Kernigs sign(+)She was alert
4、 and oriented but spoke in phrases of two to four words,rather than complete sentences.The neurologic examination otherwise revealed no abnormalities.病例病例 辅助检查辅助检查-CSF第一天第五天病例病例 辅助检查辅助检查-器械器械MRI showed a subtle hyperintensity on T2 images in both hippocampal regions and possible slight meningeal enh
5、ancement.EEG revealed generalized low-amplitude slowing and continuous focal slowing over the entire left hemisphere;no epileptiform activity病例病例 病情演变病情演变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.
6、5.When 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.定位诊断定性诊断诊断依据如何求证定义、解剖和病原学定义、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细菌性脑膜炎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)等化脓性脑膜炎化脓性脑膜炎病因和发病机制病理临
8、床表现实验室检查诊断和鉴别诊断治疗预后化脓性脑膜炎化脓性脑膜炎-病因和发病机制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、绿脓感染途径血行播散直接扩散经脑脊液化脓性脑膜炎化脓性脑膜炎-病理病理大体: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:偶见小脓肿化脓性脑膜炎化脓性脑膜炎-临床表现临床表现头痛87%发热77%颈强83%意识改
9、变69%呕吐35%惊厥5%低温或发热疲软思睡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(包括大儿童)婴幼儿感染症状:寒战,发热脑膜刺激征: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,失语其他症状:出血性皮疹脑脊液检查血象头颅MR或CT脑电图其他:血培养、皮肤瘀点培养化脓性脑膜炎化脓性脑膜炎 实验室检查实验室检查诊断:急性发病+三联征+脑脊液检查鉴别诊断: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化脓性脑膜炎 诊断和鉴别诊断诊断和鉴别诊断化脓性脑膜炎化脓性脑膜炎 治疗:抗生素治疗:抗生素基本原则全程住院静脉给药足疗程选择原则肺炎
10、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),其他(头孢曲松)李斯特菌(氨苄青);金葡(万古霉素)未确定病原菌:头孢曲松激素:地塞米松10-20mg/d3-5天补液和脱水发热惊厥脑积水隔离化脓性脑膜炎化脓性脑膜炎治疗:其他治疗:其他化脓性脑膜炎化脓性脑膜炎 预后预后病死率15%后遗症:智力减退癫痫脑积水结核性脑膜炎结核性脑膜炎病因和发病机制病理临床表现实验室检查诊断和鉴别诊断治疗预后结核性脑膜炎发病率结核性脑膜炎发病率0.35-0.7/10万万/年年结核性脑膜炎结核性脑膜炎 病因和发病机制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途径血行播散淋巴系统播散
11、局部播散结核性脑膜炎结核性脑膜炎 病理病理脑底部渗出物血管炎脑积水结核性脑膜炎结核性脑膜炎 临床表现临床表现慢性、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点的症状毒血症状:低热、盗汗、纳差、乏力、精神软脑神经损害脑室质损害结核性脑膜炎结核性脑膜炎 辅助检查辅助检查金标准: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其他:PPD皮试,血沉,血常规结核性脑膜炎结核性脑膜炎 Ahuja诊断标准诊断标准A临床:发热头痛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
12、/dl,糖60%血糖,3墨汁染色(-),肿瘤细胞(-)C影像学:有下列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TBM:A+B+C+D91.7%很可能TBM:A+(B+C+D)中的2个66.7%可能TBM:A+(B+C+D)中的1个38.5%阳性预测值(PPV)结核性脑膜炎结核性脑膜炎 诊断新方法诊断新方法Sensitivity and specificity of immunocytochemical staining of mycobacterial antigens in the cytoplasm of
13、 cerebrospinal fluid macrophages for diagnosing tuberculous meningitis.Shao Y,Xia P,Zhu T,Hu X.J Clin Microbiol.2011 Sep;49(9):3388-91.结核性脑膜炎结核性脑膜炎 鉴别诊断鉴别诊断化脓性脑膜炎病毒性脑膜炎隐球菌性脑膜炎脑膜癌病结核性脑膜炎结核性脑膜炎 治疗治疗抗痨治疗药物种类:异烟肼(H)、利福平(R)、吡嗪酰胺(Z)、乙胺丁醇(E)、链霉素(S)合用方案和疗程:常用(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、脑积水引流术结核性脑
14、膜炎结核性脑膜炎 预后预后自然病程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他脏器结核或粟粒性结核不影响预后后遗症轻重不一单纯疱疹病毒性脑炎单纯疱疹病毒性脑炎病因和发病机制病理临床表现实验室检查诊断和鉴别诊断治疗预后单疱脑炎单疱脑炎 病因和发病机制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%)途径:HSV-1:密切接触、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无免疫介导损害单疱脑炎单疱脑炎 病理病理部位出血坏死
15、炎性包涵体单疱脑炎单疱脑炎 临床表现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、疱疹单疱脑炎单疱脑炎 实验室检查实验室检查脑电图影像学脑脊液病原学病理单疱脑炎单疱脑炎 诊断诊断临床拟诊临床表现: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发现HSV特异性抗体变化脑活检单疱脑炎单疱脑炎 鉴别诊断鉴别诊断其他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)单疱脑炎单疱脑炎 治疗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单疱脑炎单疱脑炎 预后预后不治疗死亡率70-80%,阿昔洛韦治疗后降至28%预后取决于意识状况患者年龄治疗是否及时后遗症10%回到原来的病例回到原来的病例定位定位根据头痛、颈强、克氏征阳性、脑膜强化定位于软脑膜根据意识改变、失语、左右手失认、双侧海马区MRT2相高信号、脑电图异常定位于脑实质定性定性Midnight根据急性起病、发热、寒战、脑脊液细胞数增高考虑感染根据脑脊液不浑浊,白细胞数32-107,分类迅速从中性粒转化为淋巴细胞为主,首先考虑为非化脓性炎症,病毒性可能大临床印象和临床印象和Work-up脑膜脑炎:病毒性?结核性?疫源地接触史,昆虫叮咬史,病原检测