Neuroimaging and blood markers in post treatment Lyme disease with persistent neurologic symptoms

具有持续神经系统症状的莱姆病治疗后的神经影像学和血液标记物

• 批准号: 10745421
• 负责人: CHERIE L MARVEL
• 金额: $ 57.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10745421
• 关键词: Acute; Address; Affect; Aftercare; Antibiotic Therapy; Antibiotics; Axon; Bacteria; Biological Markers; Blood; Borrelia; Borrelia burgdorferi; Brain; CCL19 gene; Case Series; Central Nervous System; Clinical; Cognition; Cognitive; Control Groups; Data; Demyelinations; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Early treatment; Exhibits; Extravasation; Foundations; Functional Magnetic Resonance Imaging; Goals; Health; Impairment; Infection; Inflammation; Inflammatory; Injury; Interleukin-6; Intervention; Iron; Knowledge; Ligands; Light; Longitudinal Studies; Longitudinal cohort; Lyme Disease; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Myelin; Myelin Sheath; Neurobehavioral Manifestations; Neurobiology; Neurocognitive; Neurologic Symptoms; Outcome; Outcome Measure; Participant; Patient Outcomes Assessments; Patient-Focused Outcomes; Patients; Persons; Plasma; Process; Publishing; Radial; Recording of previous events; Reporting; Research; Risk; Structure; Symptoms; Testing; Therapeutic; Time; Water; associated symptom; axon injury; brain health; chemokine; clinical infrastructure; cognitive performance; cognitive testing; cohort; cost; diagnostic tool; disabling symptom; erythema migrans; executive function; experience; frontal lobe; healing; imaging modality; inflammatory marker; innovation; insight; multimodal neuroimaging; neural; neurofilament; neuroimaging; novel; novel diagnostics; patient stratification; persistent symptom; prevent; prognostic; prognostic indicator; prognostic tool; recruit; response; tick transmission; tool; white matter; white matter change

PROJECTSUMMARY/ABSTRACT Lyme disease is an inflammatory disease, transmitted by ticks that are infected with the bacterium Borrelia bugdorferi. Despite treatment with antibiotics, 10-20% of patients develop post-treatment Lyme disease (PTLD) that often includes neurocognitive symptoms. The mechanisms underlying this are not well understood. Prior published and preliminary data from our research group suggests that cognitive performance is impaired in PTLD and that white matter (WM) changes on functional MRI (fMRI) are part of this process. WM changes are also, however, associated with better patient-reported outcomes. Thus, WM changes during Lyme disease may be part of a healing process following injury that comes at a cost to cognition, but more information is needed. In this study, we will draw upon a unique longitudinal cohort of patients with early Lyme disease and erythema migrans who will be studied longitudinally for 12 months. Their data will be compared to that of healthy controls without a history of Lyme disease. Our overall objective is to study the underlying mechanism of neurologic symptoms in PTLD. We will test the overarching hypothesis that WM changes reflect an adaptive response, and these changes predict better outcomes after treatment of early Lyme disease. To accomplish this goal, we will track WM activity immediately after initial antibiotic therapy and longitudinally 6 and 12 months later. Functional MRI (fMRI) will be used to measure WM activity that will be compared to outcomes, which will be measured using clinical scales and cognitive testing (AIM 1). We will also address the underlying neurobiological basis of WM changes by determining whether the myelin sheath or the underlying axon, both of which comprise WM, are affected in PTLD. To do so, we will use multimodal neuroimaging measures including diffusion tensor imaging (DTI), QSM and 𝜒-separation to understand axon and myelin integrity and health. A blood plasma marker, neurofilament light chain (NfL), will be used to quantify axonal injury. These variables will be correlated with cognitive performance, clinical scales, and blood inflammation markers, which, if successful, would provide simple prognostic indicators. (AIM 2) Finally, we will examine inflammatory markers including the chemokine ligand 19 (CCL19), which has been associated with increased risk of developing PTLD, and Interleukin-6 (IL-6), which plays a role in mediating inflammation and demyelination. These have not been shown to correspond with central nervous system markers in Lyme disease thus far, but they may correspond with MRI WM values, which has never been tested. (AIM 3). Collectively, our studies represent a rigorous approach by including multimodal neuroimaging combined with blood biomarker measurement towards elucidating determinants that are associated with the cognitive and clinical outcomes of PTLD. The long-term goal is to generate insights that may lay the foundation for new diagnostic, prognostic, and therapeutic approaches to the cognitive manifestations of PTLD.

项目概要/摘要 莱姆病是一种炎症性疾病，由感染了疏螺旋体的蜱传播 bugdorferi。尽管使用抗生素治疗，但仍有10-20%的患者在治疗后发生莱姆病（PTLD） 通常包括神经认知症状这背后的机制还不清楚。之前 我们研究小组的已发表和初步数据表明，PTLD患者的认知能力受损， 功能性磁共振成像（fMRI）上的白色物质（WM）变化是这一过程的一部分。WM的变化也是， 然而，与更好的患者报告结果相关。因此，莱姆病期间WM的变化可能是 受伤后愈合过程的一部分，这是以认知为代价的，但需要更多的信息。在 这项研究，我们将利用一个独特的纵向队列的患者早期莱姆病和红斑 将对移民进行为期12个月的纵向研究。他们的数据将与健康对照组进行比较 没有莱姆病史 我们的总体目标是研究PTLD神经系统症状的潜在机制。我们将测试 总体假设，WM的变化反映了适应性反应，这些变化预测更好 早期莱姆病治疗后的结果。为了实现这一目标，我们将立即跟踪WM活动 在初始抗生素治疗后以及纵向6个月和12个月后。功能性MRI（fMRI）将用于 测量WM活动，将其与结局进行比较，将使用临床量表进行测量， 认知测试（AIM 1）。 我们还将通过确定髓磷脂是否与脑白质的变化有关， 鞘或下面的轴突，两者都包含WM，在PTLD中受到影响。为此，我们将使用 多模态神经成像测量，包括扩散张量成像（DTI），QSM和神经元分离， 了解轴突和髓鞘的完整性和健康。血浆标志物神经丝轻链（NfL）将在 用于量化轴突损伤。这些变量将与认知表现、临床量表和 血液炎症标志物，如果成功，将提供简单的预后指标。(AIM（二） 最后，我们将检查炎症标志物，包括趋化因子配体19（CCL 19）， 与发生PTLD的风险增加有关，白细胞介素-6（IL-6）在介导PTLD的发生中起作用。 炎症和脱髓鞘。这些尚未被证明与中枢神经系统相对应 迄今为止，莱姆病的标记物，但它们可能与MRI WM值，这是从来没有测试。 (AIM 3）。总的来说，我们的研究代表了一种严格的方法， 血液生物标志物测量有助于阐明与认知和 PTLD的临床结局。长期目标是产生见解，为新的 PTLD认知表现的诊断、预后和治疗方法。