CENTRAL NERVOUS SYSTEM INVASION IN EARLY LYME DISEASE

莱姆病是由螺旋体伯氏疏螺旋体 (Borrelia burgdorferi) 引起的一种主要疾病 我国新出现的感染。神经系统受累已成为 这种感染的发病率很高，但尚未得到充分研究。 由于缺乏基本的基础资料，有效的公共卫生民意调查受到阻碍 有关临床和实验室特征以及发病机制的信息 莱姆病的机制。该提案的目的是确定 中枢神经系统的频率、临床相关性和结果 早期莱姆病（CNS）感染。这项研究将重点关注 3 名成人 新感染病例组（N=100）：1）单个病灶 游走性红斑 (EM) (N=25)； 2) 多焦电镜 (N=25); 3）神经性莱姆病 疾病（N=50）。所有符合条件的患者都将与疾病控制中心会面 莱姆病的预防诊断标准。经过最初的 综合评估（评估临床症状的自我报告表， 心理社会和精神病学措施以及健康结果；皮肤、血液和 脑脊液（CSF）研究；认知评估）受试者将 接受标准抗生素治疗，然后进行前瞻性随访 18个月。对照组为健康受试者 (N=1 00) 频率与年龄、教育程度和性别相匹配；和科目 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（侵袭将通过脑脊液阳性来定义 培养物、疏螺旋体抗原、疏螺旋体 DNA 或鞘内疏螺旋体 抗体）；记录神经系统症状和健康功能状态 早期感染患者。 假设：伯氏疏螺旋体入侵中枢神经系统在早期很常见 感染。推论：早期莱姆病患者经常出现神经系统症状 疾病。推论：在该人群中，新发头痛是一种临床症状 CNS 入侵的标志物，而 CSF IgM 对伯氏疏螺旋体的反应性是 中枢神经系统侵袭的免疫标志物。 具体目标 2：检查早期神经系统受累的结果 莱姆病。 假设：感染后，患者持续存在脑脊液 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；或细胞计数或蛋白质异常）都会出现症状。 推论：脑脊液的清除与临床改善相关。 具体目标 3：确定早期莱姆病患者的比例 出现晚期脑病的人。问题：早期莱姆病的比例是多少 患者将在以下领域出现持续的神经行为功能障碍 注意力和记忆力？ 该提案将有助于表征早期莱姆病的神经系统方面 疾病，将有助于诊断和管理，并有助于指导 制定合理且具有成本效益的莱姆病医疗保健计划 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.