CENTRAL NERVOUS SYSTEM INVASION IN EARLY LYME DISEASE

早期疾病中的中枢神经系统侵袭

• 批准号: 6273873
• 负责人: PATRICIA K COYLE
• 金额: $ 15.55万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273873
• 关键词: Borrelia; Lyme disease; attention; central nervous system disorders; cerebrospinal fluid; clinical research; human subject; longitudinal human study; microorganism immunology; neurologic manifestations; neuropsychological tests; outcomes research; pathologic process

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.

莱姆病，由于螺旋体伯氏疏螺旋体，是一个主要的 在我国出现感染。神经系统受累已经成为 这种感染的发病率很高，但尚未得到充分研究。 有效的公共卫生民意调查因缺乏基本的 临床和实验室特征以及发病机制的信息 莱姆病的发病机制本建议的目的是确定 中枢神经系统损害发生率、临床相关因素及转归 (CNS)莱姆病早期感染。这项研究将集中在3个成年人 新发感染病例组（N=100）：1）单病灶 游走性红斑（EM）（N=25）; 2）多灶性EM（N=25）; 3）神经系统莱姆病 疾病（N=50）。所有符合条件的患者将符合疾病控制中心 和莱姆病预防诊断标准。经过初步 综合评估（自我报告表以评估临床症状， 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个月比较组为健康受试者（N=1 00） 频率与年龄、教育和性别的病例相匹配; 其他神经系统疾病（N=50）。 具体目标1：确定早期局部CNS侵袭的频率 和播散性莱姆病（侵袭将由阳性CSF定义 培养、疏螺旋体抗原、疏螺旋体DNA或鞘内疏螺旋体 抗体）;记录神经系统疾病和健康功能状态 早期感染患者。 假设：B侵入CNS。Burgdorferi在早期很常见。 感染推论：神经系统疾病在早期莱姆病中很常见 疾病推论：在这一人群中，新发头痛是一种临床 中枢神经系统侵袭的标志物，而脑脊液中对伯氏B菌的IgM反应性是一种 CNS侵袭免疫标志物。 具体目标2：检查神经系统受累的结果， 莱姆病 假设：感染后，持续性CSF患者 异常（定义为CNS侵袭标志物;疏螺旋体免疫 复合物;或异常细胞计数或蛋白质）将是有症状的。 推论：CSF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 患有晚期脑病的人。问题：早期莱姆的比例是多少 患者将在以下领域出现持续性神经行为功能障碍： 注意力和记忆力？ 这一建议将有助于表征早期莱姆神经方面 疾病，将有助于诊断和管理，并将有助于指导 为莱姆病制定合理和具有成本效益的医疗保健计划 疾病