神经梅毒

神经梅毒Neurosyphilis,概述,神经梅毒是由苍白密螺旋体（Treponema pallidum）感染引起的慢性传染性疾病，其病程发展缓慢，可以累及全身各个脏器和组织，包括神经系统。 抗生素应用之前西方国家成人的梅毒感染率为8%10%，其中超过40%的病例侵犯中枢神经系统。,流行病学,美国二战后梅毒发病率达到高峰（90/10万人），20世纪60年代中期处于最低点（7/10万人），7080年代约 （11/10万人），80年代因AIDS病流行和毒品泛滥，发病率急剧回升。我国人群中梅毒的发病率报道不确定，20世纪50年代华山医院皮肤科统计初诊病人中梅毒病例占4.5%。1964年以后基本未发现新的感染病例。,流行病学,近20年梅毒又卷土重来，吸毒人群中梅毒阳性率11.4%，女性达37.1%，男性检出率仅2.8%。我国有关神经梅毒的发病和患病情况如下：20 世纪80年代梅毒在我国重新出现；1991年全国报告梅毒1892例，年发病率为0.16 /10万; 1998年我国梅毒发病人数达53768例，发病率为4.31/10 万。2007年梅毒的发病数达到225601例，年发病率为17. 16 /10 万。,流行病学,HIV感染人群中神经梅毒的发病率为0.6%-16%。Ghanem等引指出CD4+淋巴细胞计数350/mm3、快速血浆反应素环状卡片试验(RPR)滴度1:128、男性、未接受高效抗逆转录病毒治疗是合并HIV感染的梅毒患者发展为神经梅毒的危险因素。,Farhi D,Dupin N.Management of syphilis in the HIV-infected patient:facts and controversiesJ.Clin Dermatol, 2010,28(5):539-545Ghanem KG,Moore RD,Rompalo AM,et a1.Neurosyphilis in a clinical cohort of HIV-1-infected patientsJ.AIDS,2008,22(10):1145-1151,流行病学,中国台湾一项研究则显示，CD4+淋巴细胞计数0.30) and a narrowing of cerebral sulcus was observed at the parietal lobes (C, arrow head), suggesting hydrocephalus.,神经梅毒的诊断,2015 年美国疾病控制中心性传播疾病诊断和治疗指南中神经梅毒诊断标准：（1）血清学检查阳性；（2）神经系统症状及体征；（3）脑脊液检查异常（脑脊液细胞计数或蛋白测定异常，加上脑脊液VDRL阳性）。,患者有神经系统症状及体征，脑脊液VDRL阳性，在排除血液污染后，可诊断神经梅毒。脑脊液VDRL 阴性，临床上出现神经梅毒的症状和体征，血清学检查阳性时，如果脑脊液细胞计数或蛋白测定异常，考虑诊断神经梅毒。也可以考虑行脑脊液FTA - ABS。脑脊液FTA - ABS 阴性，尤其对于神经系统表现没有特异性的患者，不应考虑神经梅毒。,梅毒、淋病、生殖器疱疹、生殖道沙眼衣原体感染诊疗指南(2014) 中国疾病预防控制中心性病控制中心、中华医学会皮肤性病学分会性病学组、中国医师协会皮肤科医师分会性病亚专业委员会,疑似病例： 应同时符合临床表现、实验室检查、中的脑脊液常规检查异常(排除引起异常的其他原因)，可有或无流行病学史；确诊病例： 应同时符合疑似病例的要求和实验室检查中的脑脊液梅毒血清学试验阳性。,实验室检查：非梅毒螺旋体血清学试验阳性，极少数晚期患者可阴性；梅毒螺旋体血清学试验阳性；脑脊液检查：白细胞计数5106/L，蛋白量500 mg/L，且无引起异常的其他原因。脑脊液FrA-ABS和(或) VDRL试验阳性。在没有条件做FFA-ABS和VDRL的情况下，可以用TPPA和RPR/TRUST替代。,神经梅毒的治疗,首选：静脉应用青霉素18002400万单位，分4次静脉给药（q6h），连用10-14天。病因治疗开始前1天给予类固醇激素： 强的松510mg po tid，连用3天。以防止Jarisch-Herxheimer反应。14天后给予：(长效)苄星青霉素240万单位/周 qw3周(注射用水稀释，每侧肌注120万单位)可加用丙磺舒（Probenecid）500mg qid，以增加药物浓度。,神经梅毒的治疗,青霉素过敏者给予四环素、红霉素或氯霉素、头孢曲松：四环素：500mg qid 30天；美满霉素治疗早期梅毒： 100mg bid 15天，首次加倍；红霉素： 500mg qid 30天；强力霉素：100mg tid 30天；闪电样疼痛给予卡马西平治疗.,梅毒治疗过程中的特殊反应：赫氏反应: 表现为急性发热性疾病伴头痛、肌痛、寒战和发冷,24 小时内可缓解;多见于早期梅毒,预防赫氏反应的方法是泼尼松每日20 60mg,连服3 日,在泼尼松开始治疗24 小时后开始抗梅毒治疗。,普鲁卡因反应: 表现为精神异常、躁狂、Hoigne综合征,以恐惧死亡为特征,注射后立即产生幻觉或癫痫样发作。持续不到20分钟;处置上先排除过敏反应,再进行安抚,必要时也可进行行为控制,如有抽搐,可直肠/ 静脉/ 肌内给予5-10mg 的地西泮(Diazepam),过敏性休克: 立即肾上腺素1:1000 肌注0.5ml，随后肌注/静注抗组胺药(如氯苯那敏10mg)、肌注/静注氢化可的松100mg。,神经梅毒的治疗,所有类型的神经梅毒患者： 应每3个月进行一次检查； 每间隔6个月检查一次脑脊液。如果6个月后症状消失，脑脊液异常逆转（细胞消失、蛋白、 球蛋白减少，血清学转阴），则无需进一步治疗。第9和第12个月时应进行临床检查，并在第12个月时进行腰穿检查。若脑脊液细胞和蛋白恢复正常，血清学弱阳性持续存在，也无需进行进一步治疗。,A 46-year-old woman with a 15-month history of progressive dementia and personality changes was admitted toour hospital due to generalized seizures and a prolonged disturbance of consciousness. She tested positive for syphilis with a rapid plasma reagent. Fluorescent treponemal antibody absorption, measured for confirmation, was also positive.A human immunodeficiency virus test was negative.Axial fluid-attenuated inversion recovery magnetic resonance imaging (MRI) revealed bilateral frontal and right insular cortical lesions (Picture A) in addition to a mesial temporal lesion (Picture B) (1, 2). The patient received a 14-day course of penicillin G (18 million units/day) with a gradual improvement in consciousness. The seizures were successfullycontrolled with 800 mg/day of sodium valproate. MRI showed frontal and mesial temporal atrophy three monthsafter treatment (Picture C and D).,Hitoshi Aizawa, Harumi Yomono,Hiroshi Kurisaki. Neurosyphilis Presenting as Frontal and Mesial Temporal Encephalitis. Intern Med 2013,52: 2381-2382.,A 55-year-old Caucasian man presented to our facility with acute collapse against abackground of memory difficulties over the previous six months. A magnetic resonance imaging scan of his brain revealed high T2 signal intensity and atrophy within the right frontal area in addition to high T2 signal intensity in the bilateral mesial temporal areas. Blood and cerebrospinal fluid analysis revealed an active syphilis infection. An 18F-fluorodeoxyglucose positron emission tomography brain scan showed intensely increased 18F-fluorodeoxyglucose uptake limited to the head of the right hippocampus. He responded to penicillin treatment with an improvement in his cognition, which was further reflected in a complete resolution of the findingspreviously seen on magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans.,Omer TA,Fitzgerald DE,Sheehy N,DohertyCP. Neurosyphilispresentingwithunusualhippocampalabnormalitiesonmagnetic resonance imagingandpositron emission tomography scans: a case report. J Med Case Rep.2012 Nov 21;6:389.,A 41-year-old man was found to have bilateral disc edema on a routine exam. Brain MRI was unremarkable,and lumbar puncture revealed a normal opening pressure, with an elevated cerebrospinal fluid white cell count. Orbit MRI showed optic nerve sheath expansion and enhancement, consistent with optic perineuritis. He tested positive for syphilis based on serum RPR and FTA-ABS. He was placed on IV Penicillin 3,000,000 Units every 4 hours for 14 days.Repeat testing two weeks after antibiotic treatment showedmarked improvement in both his symptoms and the extent of disc edema .Visual field testing also improvedafter antibiotics, with resolution of the enlarged blind spot.,Sarah E. Parker and John H. Pula. Neurosyphilis Presenting as Asymptomatic Optic Perine