CENTRAL NERVOUS SYSTEM INVASION IN EARLY LYME DISEASE

由伯氏疏螺旋体引起的莱姆病是一种主要的 我国新出现的感染病例。神经参与已成为 这种感染的发病率很高，但尚未得到很好的研究。 有效的公共卫生民意调查因缺乏基础设施而受阻 有关临床和实验室特征及发病机制的信息 莱姆病的发病机制。这项提案的目标是确定 中枢神经系统损害的发生频率、临床相关性及转归 早期莱姆病患者的中枢神经系统感染。这项研究将集中在3名成年人身上 新获得性感染病例组(N=100)：1)单病灶 移行性红斑(EM)(N=25)；2)多灶性EM(N=25)；3)神经性莱姆病 疾病(N=50)。所有符合条件的患者将符合疾病控制中心的要求 和莱姆病的预防诊断标准。在首字母之后 综合评估(评估临床症状的自我报告表， 心理社会和精神措施以及健康结果；皮肤、血液和 脑脊液(CSF)研究；认知评估)对象将 接受标准的抗生素治疗，然后前瞻性地进行跟踪 已经18个月了。对照组为健康受试者(N=100) 与年龄、教育程度和性别相匹配的病例； 其他神经系统疾病(N=50)。 具体目标1：确定早期局部中枢神经系统侵袭的频率 和播散性莱姆病(侵袭性将由阳性的脑脊液定义 培养、疏螺旋体抗原、疏螺旋体DNA或鞘内疏螺旋体 抗体)；记录神经主诉和健康功能状态 早期感染的患者。 假设：伯氏杆菌侵袭中枢神经系统在早期是常见的 感染。推论：早期莱姆病患者常有神经系统症状 疾病。推论：在这一人群中，新的头痛发作是临床上的 中枢神经系统侵袭的标志，而脑脊液对伯氏杆菌的IgM反应是一种 中枢神经系统侵袭的免疫标志物。 具体目标2：检查早期神经受累的结果 莱姆病。 假设：感染后，持续性脑脊液患者 异常(定义为中枢神经系统侵袭标志物；疏螺旋体免疫 复合体；或异常细胞计数或蛋白质)将是症状。 结论：脑脊液清除与临床改善有关。 具体目标3：确定早期莱姆病患者的比例 发展成晚期脑病的人。问：早期莱姆占多大比例？ 患者将在以下领域出现持续性神经行为障碍 注意力和记忆力？ 这项建议将有助于描述早期莱姆病的神经学特征。 将有助于诊断和管理，并将有助于指导 为莱姆制定合理且具有成本效益的医疗保健计划 疾病。

Lyme disease, due to the spirochete Borrelia burgdorferi, is a major emerging infection in our country. Neurologic involvement has become the significant morbidity of this infection, but has not been well studied. Effective public health poll is being hampered by lack off basic information on clinical and laboratory features and pathogenetic mechanisms of Lyme disease. The objective of this proposal is to identify the frequency, clinical correlate and outcome of central nervous system (CNS) infection in early Lyme disease. This study will focus on 3 adult case groups (N=100) with newly acquired infection: 1) single lesion erythema migrans (EM) (N=25); 2) multifocal EM (N=25); 3) neurologic Lyme disease (N=50). All eligible patient will meet Centers for Disease Control and Prevention diagnostic criteria for Lyme disease. After an initial comprehensive evaluation (self report forms to assess clinical symptoms, psychosocial and psychiatric measures, and health outcome; skin, blood and cerebrospinal fluid (CSF) studies; cognitive assessment) subjects will receive standard antibiotic treatment, and then be followed prospectively for 18 months. Comparison groups will be healthy subjects (N=1 00) frequency matched to cases on age, education and gender; and subjects with other neurologic diseases (N=50). Specific Aim 1: To determine the frequency of CNS invasion in early local and disseminated Lyme disease (invasion will be defined by positive CSF culture, Borrelial antigen, Borrelial DNA, or intrathecal Borrelial antibodies); to document neurologic complaints and health function status of early infection patients. Hypothesis: CNS invasion by B. burgdorferi is common during early infection. Corollary: neurologic complaints are frequent in early Lyme disease. Corollary: in this population new onset of headache is a clinical marker of CNS invasion, while CSF IgM reactivity to B.burgdorferi is an immune marker of CNS invasion. Specific Aim 2: To examine the outcome of neurologic involvement in,early Lyme disease. Hypothesis: Following infection, patients with persistent CSF abnormalities (defined as CNS invasion markers; Borrelial immune complexes; or abnormal cell count or protein) will be symptomatic. Corollary: clearance of CSF is associated with clinical improvement. Specific Aim 3: To determine the proportion of early Lyme disease patients who develop late encephalopathy. Question: what proportion of early Lyme patients will develop persistent neurobehavioral dysfunction in domains of attention and memory? This proposal will help characterize the neurologic aspects of early Lyme disease, will aid in diagnosis and management, and will help guide the formulation of a rational and cost effective health care program for Lyme disease.