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

项目摘要/摘要 莱姆病是一种炎症性疾病，由感染疏螺旋体细菌的壁虱传播。 伯多尔费里。尽管使用抗生素治疗，仍有10%-20%的患者在治疗后发展为莱姆病(PTLD) 这通常包括神经认知症状。这背后的机制还没有被很好地理解。之前 我们研究小组公布的初步数据表明，PTLD患者的认知能力受到损害 而功能磁共振成像(FMRI)上的白质(WM)变化是这一过程的一部分。WM的变化也是， 然而，与患者报告的更好的结果相关。因此，莱姆病期间WM的变化可能是 损伤后康复过程的一部分，是以认知为代价的，但需要更多的信息。在……里面 在这项研究中，我们将对早期莱姆病和红斑患者进行独特的纵向队列研究 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的数据进行比较 没有莱姆病病史。 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 最重要的假设是，WM的变化反映了一种适应性反应，并且这些变化更好地预测了 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 在最初的抗生素治疗之后，以及6个月和12个月后的纵向治疗。功能磁共振成像(FMRI)将用于 测量WM活动，并将其与结果进行比较，这将使用临床量表和 认知测验(AIM 1)。 我们还将通过确定髓鞘是否存在髓鞘来探讨WM变化的潜在神经生物学基础 在PTLD中，构成WM的鞘或下层轴突受到影响。为此，我们将使用 多模式神经成像方法包括扩散张量成像、QSM和𝜒分离 了解轴突和髓鞘的完整性和健康。一种血浆标志物，神经丝轻链(NFL)，将被 用于量化轴突损伤。这些变量将与认知表现、临床评分和 血液炎症标志物，如果成功，将提供简单的预后指标。(目标2) 最后，我们将检测炎症标志物，包括趋化因子配体19(CCL19)，它已经被 与PTLD和白介素6(IL-6)的发生风险增加相关，白介素6在 炎症和脱髓鞘。这些还没有被证明与中枢神经系统相对应。 到目前为止，莱姆病的标志物，但它们可能与MRI WM值相对应，这一点从未被测试过。 (目标3)。总体而言，我们的研究代表了一种严格的方法，将多模式神经成像结合在一起 通过血液生物标记物测量来阐明与认知和治疗相关的决定因素 PTLD的临床转归。长期目标是产生洞察力，为新的 PTLD认知表现的诊断、预后和治疗方法。

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.