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1、中枢神经系统螺旋体病诊疗进展 -脑脊液检查在合并感染HIV的神经梅毒患者诊断中的应用,江苏省人民医院神经内科金庆文,梅毒,梅毒是由苍白（梅毒）螺旋体引起的慢性、系统性性传播疾病。主要通过性途径传播，临床上可表现为一期梅毒、二期梅毒、三期梅毒、潜伏梅毒和先天梅毒（胎传梅毒）等。与结核、麻风并称世界三大慢性传染病。是中华人民共和国传染病防治法中，列为乙类防治管理的病种。,神经梅毒,神经梅毒(neurosyphilis) 是由苍白密螺旋体侵犯神经系统出现脑膜、大脑、血管或脊髓等损害的一组临床综合征，可发生于梅毒病程的各个阶段，往往是因为早期梅毒未经彻底治疗，常为晚期（期）梅毒全身性损害的重要表现。
2、The term “neurosyphilis” is frequently misunderstood to be synonymous with “tertiary syphilis” by health care personnel.,Neurosyphilis is simply involvement of the central nervous system (CNS) with syphilis infection. The manifestations vary, though, and are usually divided into early neurosyphilis
3、and late neurosyphilis. The late neurosyphilis manifestations usually manifest during the tertiary stage of syphilis and classically include dementia, general paresis, and tabes dorsalis, and are a result of extensive damage to the parynchema in the spinal cord or the cortical regions of the brain.,
4、流行病学,梅毒在全世界流行，据WHO估计，全球每年约有1200万新发病例，主要集中在南亚、东南亚和次撒哈拉非洲。近年来梅毒在我国增长迅速，已成为报告病例数最多的性病。所报告的梅毒中，潜伏梅毒占多数，一、二期梅毒也较为常见，先天梅毒报告病例数也在增加。,流行病学,10-50% of syphilis patients are HIV+ 15-20% of HIV+ syphilis patients have symptomatic neurosyphilis。 180,000-1.2 million cases of symptomatic neurosyphilis per year in
5、HIV+ individuals。 The United States Centers for Disease Control and Prevention (CDC) reported that the incidence rate of syphilis in HIV-infected persons was 77-fold greater than that in the general population.,Syphilis is a common co-morbidity with HIV, especially in the MSM (men who have sex with
6、men) community. MSM make up approximately 2/3 of cases of syphilis nationwide and HIV co-infection rates range from 34% in Houston to 51% in Chicago to 60% in Los Angeles and San Francisco.,Flood et al. JID 1998;177 (April),神经梅毒的疾病进程,Christina M. Marra University of Washington，Seattle, Washington, U
7、SA,临床症状(梅毒),1.获得性显性梅毒 （1）一期梅毒 （2）二期梅毒 （3）三期梅毒 2.获得性隐性梅毒 3.妊娠梅毒 4.先天性显性梅毒 （1）早期先天梅毒 （2）晚期先天梅毒 5.先天潜伏梅毒,临床症状(梅毒),患者还会伴随发烧、喉咙痛、虚弱、消瘦、脱发及头痛等全身症状全部症状会在两个月之内消失，然后进入3到15年，最长可代46年的漫长潜伏期。 潜伏期过后就是三期梅毒，有三种类型：梅毒瘤性梅毒患者全身的皮肤和脏器都会出现大小不一的树胶样肿瘤；神经性梅毒患者出现梅毒性脑膜炎，癫痫、瘫痪、痴呆接踵而至；心血管梅毒则会侵染主动脉，造成主动脉炎、动脉瘤、动脉瓣关闭不全，直至心力衰竭而死亡。,
8、初次性接触感染后的3天到3个月是一期梅毒，称为“硬下疳”，经过一段时间后会自愈； 再经过4到10个星期发展为二期梅毒，症状多样，在躯干和四肢出现对称而不瘙痒的粉红色皮疹，随后演变成斑丘疹乃至溃疡，而口腔和咽喉黏膜上也会形成泛白的疣状病灶，接触传染性极强。,Am Fam Physician. 2012;86(5):433-440.,临床症状(神经梅毒),临床常见的几种神经梅毒为：无症状性神经梅毒;脑膜神经梅毒;血管神经梅毒;脊髓痨;麻痹性痴呆;先天性神经梅毒。,临床症状(神经梅毒),无症状性神经梅毒占15-40%，病人可有脑脊液的异常。 诊断以CSF梅毒检验阳性，血清梅毒螺旋体和非梅毒螺旋体试验
9、通常也为阳性； 腰穿CSF细胞数：10-100个，蛋白50-100； 极少的CSF梅毒检验阴性而血清试验阳性，如病人CSF与梅毒相似，则按神经梅毒治疗。,Asymptomatic neurosyphilis: 15-40% of patients with syphilis will have some CSF abnormalities. Diagnosed by positive CSF VDRL; serum treponemal and non-treponemal tests usually positive as well LP: 10-100 WBC (lymphocyte pr
10、edominance), protein 50-100 Rarely CSF VDRL will be negative with positive serum tests; in that case, if the patient has a CSF consistent with syphilis, many people will treat for neurosyphilis,CDC-Neurosyphilis-Mandell: Principles and Practice of Infectious Disease, 5Th ed, pp 2476-2489.,临床症状(神经梅毒)
11、,II. Acute syphilitic meningitis: 6% of syphilis patients Typically the earliest manifestation of neurosyphilis Often associated with cranial nerve palsies, fever, HA, meningismus, and may have signs of cortical involvement CSF may be much like asymptomatic neurosyphilis or may demonstrate higher ce
12、ll counts/protein and lower glucose Serum and CSF VDRL almost always positive,急性梅毒性脑膜炎占6%，常见的症状有脑神经麻痹、发热、头痛、颈强直、脑膜刺激征阳性、和癫痫发作等，脑脊液循环受阻可出现视盘水肿及颅内压增高。可有大脑皮层的症状。 脑脊液与无症状性神经梅毒相似， 可能有更高的脑脊液细胞数和蛋白， 而糖含量低于正常； CSF和血清的梅毒检验均阳性。,CDC-Neurosyphilis-Mandell: Principles and Practice of Infectious Disease, 5Th ed,
13、pp 2476-2489.,临床症状(神经梅毒),III. Meningovascular syphilis: 10-12% of patients Syphilitic endarteritis causes infarction clinically similar to stroke, although may have a prodrome CSF: lymphocytosis, elevated protein; CSF VDRL usually positive,脑膜血管梅毒以脑膜或脑血管损害为主，占10-12%。梅毒性动脉炎可致梭状动脉瘤及脑血栓形成。常有前驱症状，临床表现与“中
14、风”相似。 脑脊液： 淋巴球增多 ，蛋白升高；脑脊液梅毒检验阳性。,CDC-Neurosyphilis-Mandell: Principles and Practice of Infectious Disease, 5Th ed, pp 2476-2489.,临床症状(神经梅毒),IV. General paresis: Relatively rare; occurs 15-20 years after initial infection Syphilitic infection of the meninges and cortex causes personality changes, pa
15、ranoia, emotional lability, eventually progressing to memory loss and dementia CSF: elevated lymphs and/or protein; VDRL usually positive in pre-HIV era but current data suggests sensitivity of 27-92%. Treponemal tests may be more sensitive but often are not standardized for use on CSF. A PCR has be
16、en developed but data on utility not known.,麻痹痴呆少见，首发感染15-20年后发病。 梅毒感染脑膜和皮层导致人格改变、偏执狂、情绪不稳、记忆力、计算力、认知力减退日趋严重，时间及空间定向力障碍，及痴呆。 脑脊液：淋巴细胞和蛋白升高；在艾滋病出现之前脑脊液梅毒检验阳性，但现在结果显示其敏感性仅为27-92%。密螺旋体试验更为敏感但在脑脊液测定中缺乏统一标准。PCR方法也被用于临床测定。,CDC-Neurosyphilis-Mandell: Principles and Practice of Infectious Disease, 5Th ed, pp 2476-2489.,临床症状(神经梅毒),V. Tabes dorsalis: Now rare; disease of posterior columns of spinal cord that occurs 18-25 years after infection. Often
